T cell-mediated Immune-Tolerance

Coordinator : J. van Meerwijk

Scientific objectives


T lymphocytes play a central role in the defence of the organism against pathogens and tumours. The mechanisms involved in the development of T cells in the thymus also cause the generation of autospecific and therefore potentially dangerous T cells. To avoid autoimmune pathology, immune-tolerance needs to be established. The group led by Dr. Paola Romagnoli, CNRS staff-scientist of our team, studies development of regulatory T cells, key-players of immune-tolerance, in the thymus.

During immune-responses to pathogens and tumours, T lymphocytes differentiate into specialised effector subsets. This differentiation is induced by the microenvironment in which the T cell is activated and controlled and stabilised by epigenetic mechanisms. The group led by Dr. Olivier Joffre, associate professor at the Toulouse University and holder of an interface contract with the Inserm, characterises the epigenetic mechanisms controlling T cell fate and plasticity.

Patients that receive allografts require life-long immunosuppressive treatment to control the T lymphocytes that otherwise would reject the grafts. To reduce this treatment and its important secondary effects, the group led by Prof. Joost van Meerwijk, Professor at the Toulouse University and TMIT-teamleader, develops innovating therapies against graft rejection that are based on the administration of regulatory T lymphocytes.

Our Projects


PROJECT 1: We study how T cell mediated immune tolerance develops in the thymus
The regulatory T cell repertoire is autospecific

In accordance with one of their main functions, we were the first to demonstrate that the repertoire of regulatory T cells is enriched in autospecific cells. This allows these cells to be activated when and where also the very dangerous autospecific T cells that cause autoimmunity are activated.

How does the thymus limit development of regulatory T cells?

The number of regulatory T cells developing in the thymus is much lower than the number of precursors with appropriate antigen-specificity. This suggests that the thymus somehow limits differentiation of regulatory T cells. We showed that limiting the number of precursors does not increase the proportion of cells differentiating into the regulatory lineage, which suggests that precursors are involved in shaping the niche.

Paradoxically increased development of regulatory T cells in autoimmune-prone mice

Regulatory T cells protect us from autoimmune pathology. Our finding that in autoimmune-prone mice more of these cells develop was therefore very surprising. Data from our lab also showed genetic control of the development of regulatory T cells. One involved locus is closely linked to the major histocompatibility locus (MHC).

Regulatory T cells migrate back to the thymus

We demonstrated that regulatory T cells activated during immune-responses migrate back to the thymus and influence induction of immune-tolerance. We are currently working on further consequences of this intriguing phenomenon.

PROJECT 2: We develop innovating therapies against graft-rejection
Regulatory T cells prevent bone-marrow allograft-rejection

We started our studies on the potential of regulatory T cells to prevent graft-rejection by assessing their capacity to favour acceptance of bone marrow grafts. We found that these cells act in a donor-specific manner to prevent rejection of bone marrow grafts.

A novel therapy against heart allograft rejection

Despite treatment with immunosuppressive drugs, heart allografts suffer from chronic rejection. We found that regulatory T cells of appropriate antigen-specificity can prevent chronic rejection of heart allografts in an experimental model. We obtained similar results with very immunogenic skin-allografts.

Regulatory T cell-therapy: a permanent solution?

In our bone marrow, skin, and heart allograft-models, we found that a single injection of regulatory T cells was sufficient to prevent rejection for prolonged periods. It appears that administered cells favoured the emergence of host regulatory T cells that prevent rejection. Thus, tolerance induced by these cells is “infectious” and should last a lifetime.

Regulatory T cells and prevention of chronic inflammation

Our team also works on a little-studied population of regulatory T cells (“CD8+CD28low”). We showed that these cells can prevent experimental colitis. We also demonstrated that the transcription factor AIRE, which allows the expression of tissue antigens in the thymus, is required for the development of the Treg that prevent colitis.

PROJECT 3 : We characterize the epigenetic mechanisms controlling T cell fate

The integrity of the organism is ensured by a tight interplay between conventional and regulatory T cells. The intercellular and environmental signals regulating their programming and crosstalk and the signalling events and transcriptional networks they induce have been extensively characterized. However, we now know that T cell identity is also largely controlled at the epigenetic level. The group led by Dr. Olivier Joffre, associate professor at the Toulouse University and holder of an interface contract with the Inserm, characterises the epigenetic mechanisms controlling T cell fate. It deciphers the role of non-coding RNAs and of several chromosomal proteins in the response of conventional and regulatory T cells to environmental signals and in the interplay between these two populations of cells.

 

 

Other information


Publications

2017

Apert, C; Romagnoli, P; van Meerwijk, J P M

IL-2 and IL-15 dependent thymic development of Foxp3-expressing regulatory T lymphocytes Journal Article

Protein Cell, 2017, ISSN: 1674-800x.

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Darrigues, J; van Meerwijk, J P M; Romagnoli, P

Age-Dependent Changes in Regulatory T Lymphocyte Development and Function: A Mini-Review Journal Article

Gerontology, 2017, ISSN: 0304-324x.

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Vuddamalay, Y; van Meerwijk, J P M

CD28neg and CD28low CD8+ regulatory T cells: Of Mice and Men Journal Article

Frontiers in immunology, doi: 10.3389/fimmu.2017.00031 , 2017.

BibTeX

2016

Decque, A *; Joffre, O *; Magalhaes, J G *; Cossec, J C *; Blecher-Gonen, R; Lapaquette, P; Silvin, A; Manel, N; Joubert, P E; Seeler, J S; Albert, M L; Amit, I; Amigorena, S; Dejean, A

Sumoylation coordinates the repression of inflammatory and anti-viral gene-expression programs during innate sensing Journal Article

Nat Immunol, 17 (2), pp. 140-9, 2016, ISSN: 1529-2908.

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Vuddamalay, Y; Attia, M; Vicente, R; Pomie, C; Enault, G; Leobon, B; Joffre, O; Romagnoli, P; van Meerwijk, J P

Mouse and human CD8(+) CD28(low) regulatory T lymphocytes differentiate in the thymus Journal Article

Immunology, 148 (2), pp. 187-96, 2016, ISSN: 1365-2567 (Electronic) 0019-2805 (Linking).

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2015

Thiault, N; Darrigues, J; Adoue, V; Gros, M; Binet, B; Perals, C; Leobon, B; Fazilleau, N; Joffre, O P; Robey, E A; van Meerwijk, J P M; Romagnoli, P

Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors Journal Article

Nature Immunol, 16 , pp. 628–634, 2015.

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2013

Pasquet, L; Douet, J Y; Sparwasser, T; Romagnoli, P; van Meerwijk, J P M

Long-term prevention of chronic allograft rejection by regulatory T-cell immunotherapy involves host Foxp3-expressing T cells Journal Article

Blood, 121 (21), pp. 4303-10, 2013, ISSN: 1528-0020 (Electronic) 0006-4971 (Linking).

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Tellier, J; Andrianjaka, A; Vicente, R; Thiault, N; Enault, G; Garchon, H J; van Meerwijk, J P M; Romagnoli, P

Increased thymic development of regulatory T cells in NOD mice is functionally dissociated from type I diabetes susceptibility Journal Article

Eur J Immunol, 43 (5), pp. 1356-62, 2013, ISSN: 1521-4141 (Electronic) 0014-2980 (Linking).

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2012

Romagnoli, P; Dooley, J; Enault, G; Vicente, R; Malissen, B; Liston, A; van Meerwijk, J P M

The thymic niche does not limit development of the naturally diverse population of mouse regulatory T lymphocytes Journal Article

Journal of Immunology, 189 (8), pp. 3831-7, 2012, ISSN: 1550-6606 (Electronic) 0022-1767 (Linking).

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2011

Nouzé, C; Pasquet, L; van Meerwijk, J P M

In vitro expansion of alloantigen-specific regulatory T cells and their use in prevention of allograft-rejection Book Chapter

Kassiotis, G; Liston, A (Ed.): Regulatory T-Cells: Methods and Protocols, 707 , pp. 187-196, Springer, 2011.

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Pasquet, Lise ; Joffre, Olivier ; Santolaria, Thibault ; van Meerwijk, Joost

Hematopoietic chimerism and transplantation tolerance: a role for regulatory T cells Journal Article

Frontiers in Immunology, 2 , 2011, ISSN: 1664-3224.

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Pomie, C; Vicente, R; Vuddamalay, Y; Ardesjö Lundgren, B; van der Hoek, M; Enault, G; Kagan, J; Fazilleau, N; Scott, H S; Romagnoli, P; van Meerwijk, J P M

AIRE-deficient CD8+CD28low regulatory T lymphocytes fail to control experimental colitis Journal Article

Proceedings of the National Academy of Sciences of the U.S.A., 108 (30), pp. 12437-12442, 2011.

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2010

Romagnoli, P; van Meerwijk, J P M

Thymic selection and lineage commitment of CD4+Foxp3+ regulatory T lymphocytes Journal Article

Prog Mol Biol Transl Sci., 92 , pp. 251-77, 2010.

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2008

Joffre, O; Santolaria, T; Calise, D; Al Saati, T; Hudrisier, D; Romagnoli, P; van Meerwijk, J P M

Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes Journal Article

Nature Medicine, 14 (1), pp. 88-92, 2008.

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Joffre, O; Santolaria, T; van Meerwijk, J P M

[Tregs-based immunotherapy: an efficient way to fully inhibit acute and chronic rejection.] Journal Article

Med Sci (Paris), 24 (8-9), pp. 689-691, 2008, ISSN: 0767-0974 (Print).

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Pomie, C; Menager-Marcq, I; van Meerwijk, J P M

Murine CD8(+) regulatory T lymphocytes: The new era Journal Article

Hum Immunol, 69 , pp. 708-714, 2008, ISSN: 0198-8859 (Print).

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Romagnoli, P; Ribot, J; Tellier, J; van Meerwijk, J P M

Thymic and peripheral generation of CD4+Foxp3+ regulatory T cells Book Chapter

Jiang, S (Ed.): Regulatory T cells and clinical application, in press , Springer, 2008, ISBN: 978-0-387-77908-9.

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2007

Ribot, J; Enault, G; Pilipenko, S; Huchencq, A; Calise, M; Hudrisier, D; Romagnoli, P; van Meerwijk, J P M

Shaping of the autoreactive regulatory T cell repertoire by thymic cortical positive selection Journal Article

J. Immunol., 179 , pp. 6741-6748, 2007.

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2006

Joffre, O; van Meerwijk, J P M

CD4+CD25+ regulatory T lymphocytes in bone marrow transplantation Journal Article

Seminars in Immunology, 18 (2), pp. 128-135, 2006.

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Menager-Marcq, I; Pomie, C; Romagnoli, P; van Meerwijk, J P M

CD8+CD28- regulatory T lymphocytes prevent experimental inflammatory bowel disease in mice Journal Article

Gastroenterology, 131 (6), pp. 1775-85, 2006.

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Ribot, J; Romagnoli, P; van Meerwijk, J P M

Agonist ligands expressed by thymic epithelium enhance positive selection of regulatory T lymphocytes from precursors with a normally diverse TCR-repertoire Journal Article

J. Immunol., 177 (2), pp. 1101-1107, 2006.

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Tellier, J; van Meerwijk, J P M; Romagnoli, P

An MHC-linked locus modulates thymic differentiation of CD4+CD25+Foxp3+ regulatory T lymphocytes Journal Article

Int Immunol, 18 (11), pp. 1509-1519, 2006.

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2005

Romagnoli, P; Hudrisier, D; van Meerwijk, J P M

Molecular signature of recent thymic selection events on effector and regulatory CD4+ T lymphocytes Journal Article

Journal of Immunology, 175 , pp. 5751-5758, 2005.

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Romagnoli, P; Tellier, J; van Meerwijk, J P M

Genetic control of thymic development of CD4+CD25+FoxP3+ regulatory T lymphocytes Journal Article

Eur J Immunol, 35 , pp. 3525-3532, 2005.

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2004

Cannarile, M A; Decanis, N; van Meerwijk, J P; Brocker, T

The role of dendritic cells in selection of classical and nonclassical CD8+ T cells in vivo Journal Article

J Immunol, 173 (8), pp. 4799-805, 2004.

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Joffre, O; Gorsse, N; Romagnoli, P; Hudrisier, D; van Meerwijk, J P M

Induction of antigen-specific tolerance to bone-marrow allografts with CD4+CD25+ T lymphocytes Journal Article

Blood, 103 (11), pp. 4216-4221, 2004.

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2003

Capone, M; Lees, R L; Finke, D; Ernst, B; van Meerwijk, J P M; MacDonald, H R

Selective absence of CD8+ TCRalpha beta+ intestinal epithelial cells in transgenic mice expressing beta2-microglobulin-associated ligands exclusively on thymic cortical epithelium. Journal Article

Eur J Immunol, 33 (6), pp. 1471-7, 2003.

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Cemerski, S; van Meerwijk, J P M; Romagnoli, P

Oxidative stress-induced T lymphocyte hyporesponsiveness is caused by structural modification rather than proteasomal degradation of crucial signaling molecules Journal Article

Eur J Immunol, 33 (8), pp. 2178-85, 2003.

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Doucey, MA ; Legler, DF ; Faroudi, M; Boucheron, N; Baumgaertner, P; Naeher, D; Cebecauer, M; Hudrisier, D; Rüegg, C; Palmer, E; Valitutti, S; Bron, C; Luescher, IF

Beta1 and Beta3 Integrins promote T Cell Receptor-mediated Cytotoxic T Lymphocyte Activation Journal Article

J. Biol. Chem., 278 (29), pp. 26983-91, 2003.

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Hudrisier, D; Feau, S; Bonnet, V; Romagnoli, P; van Meerwijk, J P M

In vivo maintenance of T lymphocyte unresponsiveness induced by thymic medullary epithelium requires antigen presentation by radioresistant cells Journal Article

Immunology, 108 , pp. 24-31, 2003.

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2002

Cemerski, S; Cantagrel, A; van Meerwijk, J P M; Romagnoli, P

Reactive oxygen species differentially affect T cell receptor signaling pathways Journal Article

Journal of Biological Chemistry, 277 , pp. 19585-19593, 2002.

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Constantin, A; Lauwers-Cances, V; Navaux, F; Abbal, M; van Meerwijk, J; Mazieres, B; Cambon-Thomsen, A; Cantagrel, A

Collagenase-1 (MMP-1) and HLA-DRB1 gene polymorphisms in rheumatoid arthritis: a prospective longitudinal study Journal Article

J Rheumatol, 29 (1), pp. 15-20, 2002.

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Constantin, A; Lauwers-Cances, V; Navaux, F; Abbal, M; van Meerwijk, J; Mazieres, B; Cambon-Thomsen, A; Cantagrel, A

Stromelysin 1 (matrix metalloproteinase 3) and HLA-DRB1 gene polymorphisms: Association with severity and progression of rheumatoid arthritis in a prospective study Journal Article

Arthritis Rheum, 46 (7), pp. 1754-62, 2002.

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Espinosa, E; Tabiasco, J; Hudrisier, D; Fournie, J J

Synaptic transfer by human gamma delta T cells stimulated with soluble or cellular antigens Journal Article

J Immunol, 168 (12), pp. 6336-43., 2002.

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Hudrisier, D; Bongrand, P

Intercellular transfer of antigen-presenting cell determinants onto T cells: molecular mechanisms and biological significance Journal Article

Faseb J, 16 (6), pp. 477-86., 2002.

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Romagnoli, P; Hudrisier, D; van Meerwijk, J P M

Preferential recognition of self-antigens despite normal thymic deletion of CD4+CD25+ regulatory T cells Journal Article

Journal of Immunology, 168 , pp. 1644-1648, 2002.

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Tabiasco, J; Espinosa, E; Hudrisier, D; Joly, E; Fournie, J J; Vercellone, A

Active trans-synaptic capture of membrane fragments by natural killer cells Journal Article

Eur J Immunol, 32 (5), pp. 1502-8., 2002.

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2001

Capone, M; Romagnoli, P; Beermann, F; MacDonald, H R; van Meerwijk, J P M

Dissociation of thymic positive and negative selection in transgenic mice expressing major histocompatibility complex class I molecules exclusively on thymic cortical epithelial cells Journal Article

Blood, 97 (5), pp. 1336-1342, 2001.

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Constantin, A; Navaux, F; Lauwers-Cances, V; Abbal, M; van Meerwijk, J P M; Mazières, B; Cambon-Thomsen, A; Cantagrel, A

Interferon gamma gene polymorphism and susceptibility to, and severity of, rheumatoid arthritis Journal Article

The Lancet, 358 , pp. 2051-2052, 2001.

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Hudrisier, D

Pleiotropic effects of post-translational modifications on the fate of viral glycopeptides as cytotoxic T cell epitopes Journal Article

Journal of Biological Chemistry, 276 (41), pp. 38255-60, 2001.

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Hudrisier, D

Structural and functional identification of major histocompatibility complex class I-restricted self-peptides as naturally occurring molecular mimics of viral antigens. Possible role in CD8+ T cell-mediated, virus-induced autoimmune disease Journal Article

Journal of Biological Chemistry, 276 (22), pp. 19396-403, 2001.

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Hudrisier, D; Riond, J; Gairin, JE

Molecular and functional dissection of the H-2Db-restructed subdominant cytotoxic T cell response to lymphocytic choriomeningitis virus Journal Article

J. Virol., 75 , pp. in press, 2001.

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Hudrisier, D; Riond, J; Mazarguil, H; Gairin, J E; Joly, E

CTL rapidly capture membrane fragments from target cells in a TCR signalling-dependent manner Journal Article

Journal of Immunology, 166 (6), pp. 3645-3649, 2001.

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Romagnoli, P; Strahan, D; Pelosi, M; Cantagrel, A; van Meerwijk, J P M

A potential role for tyrosine kinase p56lck in rheumatoid arthritis synovial fluid T lymphocyte hyporesponsiveness Journal Article

International Immunology, 13 (3), pp. 305-312, 2001.

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2000

Fisch, P; Mills, K H G; van Meerwijk, J P M

Molecular determinants of T-cell immunity Journal Article

The immunologist, 8 (4 & 5), pp. 114-118, 2000.

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Hudrisier, D; Luescher, I F

Antigen recognition by CD8+ CTLs Book Chapter

Sitkovsky, M V; Henkart, P A (Ed.): Cytotoxic cells: basic mechanisms and medical applications, pp. 25-43, Lippincott Williams & Wilkins, Philadelphia, 2000.

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1999

Cantagrel, A; Constantin, A; Vincent, C; Abbal, M; Laroche, M; Ohayon, E; Serre, G; Mazieres, B

Rheumatoid factor and antikeratin antibody are independent from presence of DR4 or DR1 in rheumatoid arthritis Journal Article

Rev Rhum Engl Ed, 66 (1), pp. 20-3, 1999.

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Cantagrel, A; Navaux, F; Loubet-Lescoulie, P; Nourhashemi, F; Enault, G; Abbal, M; Constantin, A; Laroche, M; Mazieres, B

Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis Journal Article

Arthritis Rheum, 42 (6), pp. 1093-100, 1999.

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Hudrisier, D; Riond, J; Mazarguil, H; Oldstone, M B A; Gairin, J E

Genetically encoded and post-translationally modified forms of a major histocompatibility complex class I-restricted antigen bearing a glycosylation motif are independently processed and co-presented to cytotoxic T lymphocytes. Journal Article

J. Biol. Chem., 274 , pp. 36274-36280, 1999.

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Marguerat, S; MacDonald, H R; Kraehenbuhl, J P; van Meerwijk, J P M

Protection from radiation-induced colitis requires MHC class II antigen expression by cells of hemopoietic origin Journal Article

Journal of Immunology, 163 (7), pp. 4033-40, 1999.

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Oldstone, M B; von Herrath, M; Lewicki, H; Hudrisier, D; Whitton, J L; Gairin, J E

Use of a high-affinity peptide that aborts MHC-restricted cytotoxic T lymphocyte activity against multiple viruses in vitro and virus-induced immunopathologic disease in vivo Journal Article

Virology, 256 (2), pp. 246-57, 1999.

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Radtke, F; Wilson, A; Stark, G; Bauer, M; van Meerwijk, J P M; MacDonald, H R; Aguet, M

Impaired T-cell fate specification in mice with an induced inactivation of Notch-1 Journal Article

Immunity, 10 , pp. 547-558, 1999.

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Romagnoli, P; Bron, C

Defective TCR signaling events in glycosylphosphatidylinositol-deficient T cells derived from paroxysmal nocturnal hemoglobinuria patients Journal Article

International Immunology, 11 (9), pp. 1411-22, 1999.

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van Meerwijk, J P M; MacDonald, H R

In vivo T lymphocyte tolerance in the absence of thymic clonal deletion mediated by haematopoietic cells Journal Article

Blood, 93 (11), pp. 3856-3862, 1999.

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1998

Cantagrel, A; Lambert, N; Alam, A

T cell receptor gene in synovial tissues of rheumatoid arthritis Journal Article

Int Rev Immunol, 17 (5-6), pp. 323-37, 1998.

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Constantin, A; Loubet-Lescoulie, P; Lambert, N; Yassine-Diab, B; Abbal, M; Mazieres, B; de Preval, C; Cantagrel, A

Antiinflammatory and immunoregulatory action of methotrexate in the treatment of rheumatoid arthritis: evidence of increased interleukin-4 and interleukin-10 gene expression demonstrated in vitro by competitive reverse transcriptase-polymerase chain reaction Journal Article

Arthritis Rheum, 41 (1), pp. 48-57, 1998.

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Hudrisier, D; Gairin, J E

Peptide-major histocompatibility complex class I complex: from the structural and molecular basis to pharmacological principles and therapeutic applications Journal Article

Curr Top Microbiol Immunol, 232 , pp. 75-97, 1998.

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Hudrisier, D; Kessler, B; Valitutti, S; Horvath, C; Cerottini, J C; Luescher, I F

The efficiency of antigen recognition by CD8+ CTL clones is determined by the frequency of serial TCR engagement Journal Article

J Immunol, 161 (2), pp. 553-62, 1998.

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Kessler, B; Hudrisier, D; Schroeter, M; Tschopp, J; Cerottini, J C; Luescher, I F

Peptide modification or blocking of CD8, resulting in weak TCR signaling, can activate CTL for Fas- but not perforin-dependent cytotoxicity or cytokine production Journal Article

J Immunol, 161 (12), pp. 6939-46, 1998.

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Lambert, N; Lescoulie, P L; Yassine-Diab, B; Enault, G; Mazieres, B; De Preval, C; Cantagrel, A

Substance P enhances cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) expression on cultured rheumatoid fibroblast-like synoviocytes Journal Article

Clin Exp Immunol, 113 (2), pp. 269-75, 1998.

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L'Faqihi, F E; Praud, C; Yassine-Diab, B; Enault, G; Lakhdar-Ghazal, F; de Preval, C; Coppin, H

Residue 67 in the DRbeta1*0101 and DRbeta1*0103 chains strongly influences antigen presentation and DR-peptide molecular complex conformation Journal Article

Tissue Antigens, 51 (1), pp. 10-9, 1998, ISSN: 0001-2815 (Print).

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van Meerwijk, J P M; Bianchi, T; Marguerat, S; MacDonald, H R

Thymic lineage commitment rather than selection causes genetic variations in size of CD4 and CD8 compartments Journal Article

J. Immunol., 160 (8), pp. 3649-54, 1998.

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van Meerwijk, J P M; Marguerat, S; MacDonald, H R

Homeostasis limits the development of mature CD8+ but not CD4+ thymocytes Journal Article

J. Immunol., 160 (6), pp. 2730-4, 1998.

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1997

Germain, R N; Bikoff, E K; Bonifacino, J; Han, R; Castellino, F; Romagnoli, P; Zhong, G M

Invariant chain regulation of MHC class II function in the secretory and endocytic pathways Journal Article

In: HLA and disease-The molecular basis, Svejgaard A. et al. (eds.), Alfred benzon Symposium, 40 , pp. 114-127, 1997.

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Hudrisier, D; Oldstone, M B; Gairin, J E

The signal sequence of lymphocytic choriomeningitis virus contains an immunodominant cytotoxic T cell epitope that is restricted by both H- 2D(b) and H-2K(b) molecules Journal Article

Virology, 234 (1), pp. 62-73, 1997.

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Kessler, B; Hudrisier, D; Cerottini, J C; Luescher, I F

Role of CD8 in aberrant function of cytotoxic T lymphocytes Journal Article

J Exp Med, 186 (12), pp. 2033-8, 1997.

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Romagnoli, P; Bron, C

Phosphatidylinositol-based glycolipid-anchored proteins enhance proximal TCR signaling events Journal Article

J Immunol, 158 (12), pp. 5757-64, 1997.

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Saadawi, A M; L'Faqihi, F; Diab, B Y; Sol, M A; Enault, G; Coppin, H; Cantagrel, A; Biesinger, B; Fleckenstein, B; Thomsen, M

Dominant clones in immortalized T-cell lines from rheumatoid arthritis synovial membranes Journal Article

Tissue Antigens, 49 (5), pp. 431-7, 1997.

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van Meerwijk, J P M; Marguerat, S; Lees, R K; Germain, R N; Fowlkes, B J; MacDonald, H R

Quantitative impact of thymic clonal deletion on the T cell repertoire Journal Article

J. Exp. Med., 185 (3), pp. 377-83, 1997.

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Zhong, G; Romagnoli, P; Germain, R N

Related leucine-based cytoplasmic targeting signals in invariant chain and major histocompatibility complex class II molecules control endocytic presentation of distinct determinants in a single protein Journal Article

J Exp Med, 185 (3), pp. 429-38, 1997.

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1996

Alam, A; Lambert, N; Lule, J; Coppin, H; Mazieres, B; de Preval, C; Cantagrel, A

Persistence of dominant T cell clones in synovial tissues during rheumatoid arthritis Journal Article

J Immunol, 156 (9), pp. 3480-5, 1996.

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Germain, R N; Castellino, F; Han, R; Reis e Sousa, C; Romagnoli, P; Sadegh-Nasseri, S; Zhong, G M

Processing and presentation of endocytically acquired protein antigens by MHC class II and class I molecules Journal Article

Immunol Rev, 151 , pp. 5-30, 1996.

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Huang, L Y; van Meerwijk, J P; Bikoff, E K; Germain, R N

Comparison of thymocyte development in normal and invariant chain- deficient mice provides evidence that maturation-related changes in TCR and co-receptor levels play a critical role in cell fate Journal Article

Int Immunol, 8 (9), pp. 1429-40, 1996.

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Hudrisier, D; Mazarguil, H; Laval, F; Oldstone, M B A; Gairin, J E

Binding of viral antigens to major histocompatibility complex class I H- 2Db molecules is controlled by dominant negative elements at peptide non-anchor residues. Implications for peptide selection and presentation Journal Article

J Biol Chem, 271 (30), pp. 17829-36, 1996.

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Zhong, G; Castellino, F; Romagnoli, P; Germain, R N

Evidence that binding site occupancy is necessary and sufficient for effective major histocompatibility complex (MHC) class II transport through the secretory pathway redefines the primary function of class II-associated invariant chain peptides (CLIP) Journal Article

J Exp Med, 184 (5), pp. 2061-6, 1996.

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1995

Gairin, J E; Mazarguil, H; Hudrisier, D; Oldstone, M B

Optimal lymphocytic choriomeningitis virus sequences restricted by H- 2Db major histocompatibility complex class I molecules and presented to cytotoxic T lymphocytes Journal Article

J Virol, 69 (4), pp. 2297-305, 1995.

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Hudrisier, D; Mazarguil, H; Oldstone, M B; Gairin, J E

Relative implication of peptide residues in binding to major histocompatibility complex class I H-2Db: application to the design of high-affinity, allele-specific peptides Journal Article

Mol Immunol, 32 (12), pp. 895-907, 1995.

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Oldstone, M B; Lewicki, H; Borrow, P; Hudrisier, D; Gairin, J E

Discriminated selection among viral peptides with the appropriate anchor residues: implications for the size of the cytotoxic T- lymphocyte repertoire and control of viral infection Journal Article

J Virol, 69 (12), pp. 7423-9, 1995.

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Romagnoli, P; Germain, R N

Inhibition of invariant chain (Ii)-calnexin interaction results in enhanced degradation of Ii but does not prevent the assembly of alpha beta Ii complexes Journal Article

J Exp Med, 182 (6), pp. 2027-36, 1995.

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Roth, M P; Malfroy, L; Offer, C; Sevin, J; Enault, G; Borot, N; Pontarotti, P; Coppin, H

The human myelin oligodendrocyte glycoprotein (MOG) gene: complete nucleotide sequence and structural characterization Journal Article

Genomics, 28 (2), pp. 241-50, 1995, ISSN: 0888-7543 (Print).

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van Meerwijk, J P M; O. Connell, E M; Germain, R N

Evidence for lineage commitment and initiation of positive selection by thymocytes with intermediate surface phenotypes Journal Article

J. Immunol., 154 (12), pp. 6314-23, 1995.

BibTeX

1994

Pascolo, E; Hudrisier, D; Sproat, B; Nguyen, T T; Toulme, J J

Relative contribution of photo-addition, helper oligonucleotide and RNase H to the antisense effect of psoralen-oligonucleotide conjugates, on in vitro translation of Leishmania mRNAs Journal Article

Biochim Biophys Acta, 1219 (1), pp. 98-106, 1994.

BibTeX

Romagnoli, P; Castellino, F; Germain, R N

Regulation of MHC class II intracellular transport and peptide loading Journal Article

In: Antigen processing and Presentation. R. E. Humphreys and S. K. Pierce (eds.), Academic Press Inc, pp. 109-123, 1994.

BibTeX

Romagnoli, P; Germain, R N

The CLIP region of invariant chain plays a critical role in regulating major histocompatibility complex class II folding, transport, and peptide occupancy Journal Article

J Exp Med, 180 (3), pp. 1107-13, 1994.

BibTeX

van Meerwijk, J P; Germain, R N

The different roles of MHC class recognition in thymocyte CD4 versus CD8 lineage commitment and positive selection Journal Article

Semin Immunol, 6 (4), pp. 231-9, 1994.

BibTeX

1993

Bikoff, E K; Huang, L Y; Episkopou, V; van Meerwijk, J; Germain, R N; Robertson, E J

Defective major histocompatibility complex class II assembly, transport, peptide acquisition, and CD4+ T cell selection in mice lacking invariant chain expression Journal Article

J Exp Med, 177 (6), pp. 1699-712, 1993.

BibTeX

Romagnoli, P; Layet, C; Yewdell, J; Bakke, O; Germain, R N

Relationship between invariant chain expression and major histocompatibility complex class II transport into early and late endocytic compartments Journal Article

J Exp Med, 177 (3), pp. 583-96, 1993.

BibTeX

van Meerwijk, J P; Germain, R N

Development of mature CD8+ thymocytes: selection rather than instruction? Journal Article

Science, 261 (5123), pp. 911-5, 1993.

BibTeX

1992

Asselbergs, F A; van Someren, P; van Meerwijk, J

Endogenous gene and amplifiable cDNA construct both produce unstable t- PA mRNA in Bowes melanoma cells Journal Article

J Biotechnol, 23 (2), pp. 143-51, 1992.

BibTeX

Romagnoli, P; Spinas, G A; Sinigaglia, F

Gold-specific T cells in rheumatoid arthritis patients treated with gold Journal Article

J Clin Invest, 89 (1), pp. 254-8, 1992.

BibTeX

1991

Guttinger, M; Romagnoli, P; Vandel, L; Meloen, R; Takacs, B; Pink, J R; Sinigaglia, F

HLA polymorphism and T cell recognition of a conserved region of p190, a malaria vaccine candidate Journal Article

Int Immunol, 3 (9), pp. 899-906, 1991.

BibTeX

Romagnoli, P; Labhardt, A M; Sinigaglia, F

Selective interaction of Ni with an MHC-bound peptide Journal Article

Embo J, 10 (6), pp. 1303-6, 1991.

BibTeX

Sinigaglia, F; Romagnoli, P; Guttinger, M; Takacs, B; Pink, J R

Selection of T cell epitopes and vaccine engineering Journal Article

Methods Enzymol, 203 , pp. 370-86, 1991.

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van Meerwijk, J P; Iglesias, A; Hansen-Hagge, T; Bluethmann, H; Steinmetz, M

Allelic exclusion of a T cell receptor-beta minilocus Journal Article

J Immunol, 147 (9), pp. 3224-8, 1991.

BibTeX

van Meerwijk, J P M; Romagnoli, P; Iglesias, A; Bluethmann, H; Steinmetz, M

Allelic exclusion at DNA rearrangement level is required to prevent coexpression of two distinct T cell receptor beta genes Journal Article

J Exp Med, 174 (4), pp. 815-9, 1991.

BibTeX

1990

Romagnoli, P; Takacs, B; Kilgus, J; Pink, J R; Sinigaglia, F

Peptide-MHC interaction: a rational approach to vaccine design Journal Article

Int Rev Immunol, 6 (1), pp. 61-73, 1990.

BibTeX

Sinigaglia, F; Guttinger, M; Romagnoli, P; Takacs, B

Malaria antigens and MHC restriction Journal Article

Immunol Lett, 25 (1-3), pp. 265-70, 1990.

BibTeX

van Meerwijk, J P; Bluthmann, H; Steinmetz, M

T-cell specific rearrangement of T-cell receptor beta transgenes in mice Journal Article

Embo J, 9 (4), pp. 1057-62, 1990.

BibTeX

1989

Kilgus, J; Romagnoli, P; Guttinger, M; Stuber, D; Adorini, L; Sinigaglia, F

Vaccine T-cell epitope selection by a peptide competition assay Journal Article

Proc Natl Acad Sci U S A, 86 (5), pp. 1629-33, 1989.

BibTeX

Sinigaglia, F; Kilgus, J; Romagnoli, P; Guttinger, M; Pink, J R

Peptide binding to MHC class II molecules: application to vaccine design Journal Article

In: Progress in Immunology, Melchers et al. (eds.), VII Springer-Verlag, pp. 1137-1143, 1989.

BibTeX

1988

Antozzi, C; Gemma, M; Baggi, F; Romagnoli, P; Peluchetti, D; Sghirlanzoni, A; Cornelio, F

Use of immmunoadsorbent columns for antiAChR antibodies removal from plasma of myasthenia gravis patients Journal Article

Plsma Ther Transf Technol, 9 , pp. 73-76, 1988.

BibTeX

Mantegazza, R; Pareyson, D; Baggi, F; Romagnoli, P; Peluchetti, D; Sghirlanzoni, A; Cornelio, F

Anti AChR antibody: relevance to diagnosis and clinical aspects of myasthenia gravis Journal Article

Ital J Neurol Sci, 9 (2), pp. 141-5, 1988.

BibTeX

1987

Cournot-Witmer, G; Bourdeau, A; Lieberherr, M; Thil, C L; Plachot, J J; Enault, G; Bourdon, R; Balsan, S

Bone modeling in gallium nitrate-treated rats Journal Article

Calcif Tissue Int, 40 (5), pp. 270-5, 1987, ISSN: 0171-967X (Print).

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1986

Plachot, J J; Thil, C L; Enault, G; Halpern, S; Cournot-Witmer, G; Balsan, S

Mitochondrial calcium and bone mineralization in the rat fetus Journal Article

Bone Miner, 1 (2), pp. 157-66, 1986, ISSN: 0169-6009 (Print).

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1978

Enault, G; Beunaiche, M; Robert, H G

[Tubal sterility: Disturbances in haemostasis and cardiac arrest during the shirodkar manoeuvre (author's transl)] Journal Article

Nouv Presse Med, 7 (10), pp. 827-30, 1978, ISSN: 0301-1518 (Print).

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1977

Boury-Heyler, C; Enault, G

[Chronic suppuration of the breast] Journal Article

J Gynecol Obstet Biol Reprod (Paris), 6 (5), pp. 625-31, 1977, ISSN: 0368-2315 (Print).

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Impact on the society

A better understanding of the development of T lymphocytes and their differentiation upon aggression by pathogens or tumours will lead to development of more specific and effective innovating therapies against e.g. immunopathologies. The regulatory T cell-based therapy against allograft-rejection developed by our team is an excellent example.

The TMIT team is also much involved in immunology-teaching at the Toulouse University. Its members teach courses at distinct academic levels, direct the Master program in Immunology and Infectious Diseases, and train PhD-students.

Agence nationale de la recherche

Agence nationale de la recherche

Fondation de recherche médicale

Fondation de recherche médicale

Région Occitanie

Région Occitanie

Fondation ARC

Fondation ARC

Ligue contre le cancer

Ligue contre le cancer