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T cells in autoimmune diseases of the CNS: migration, functions and regulation



Our aim is to better understand the cellular and molecular determinants leading to inflammation and autoimmunity in the central nervous system (CNS).

To this end we have gathered unique experimental models as well as biological samples from patients. We wish to study the transmigration and effector functions of T cells, notably CD8 T cells, using several animal models of CNS autoimmunity that we have recently developed in the laboratory. We use a model for immune-mediated narcolepsy and a model for paraneoplastic neurological diseases. Validation of the pathways identified using biological samples from patients is the next logical step.

Some auto reactive T cells express TCR recognising several self-antigens. For instance in C57BL/6 mice, a third of MOG-specific CD4 T cells also recognise neurofilament medium. We investigate the dynamics of the bi-reactive T cell response: the timing and location of their priming, expansion and avidity-maturation, and their relative dominance during disease induction and chronicity. Furthermore, using adoptive transfer and specific tolerance induction strategies we will directly assess the pathogenicity of MOG mono vs. MOG / NF-M bi-specific T cells. Lastly, we will address how immune tolerance is imposed on T cells that co-recognize 2 unrelated neural self-antigens. These studies aim to better delineate how polyspecificity of T cells impacts on induction and regulation of an organ-specific autoimmune disease.


Selected publications

Bernard-Valnet R, Yshii L, Quériault C, Nguyen XH, Arthaud S, Rodrigues M, Canivet A, Morel AL, Matthys A, Bauer J, Pignolet B, Dauvilliers Y, Peyron C, Liblau RS.
CD8 T cell-mediated killing of orexinergic neurons induces a narcolepsy-like phenotype in mice.
Proc Natl Acad Sci U S A. 2016 Sep 27.

Yshii LM, Gebauer CM, Pignolet B, Mauré E, Quériault C, Pierau M, Saito H, Suzuki N, Brunner-Weinzierl M, Bauer J, Liblau RS
CTLA4 blockade elicits paraneoplastic neurological disease in a mouse model.
Brain. 2016 Sep 6.

Martin-Blondel G, Brassat D, Bauer J, Lassmann H, Liblau RS.
CCR5 blockade for neuro-inflammatory diseases: above and beyond HIV control.
Nat Rev Neurol. 2016 Feb.

Liblau RS, Vassalli A, Seifinejad A, Tafti M
Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy
Lancet Neurol. 2015 Mar;14(3):318-28. doi: 10.1016/S1474-4422(14)70218-2.

 


Last updated November 9, 2016


Centre de physiopathologie de Toulouse Purpan - CHU Purpan - BP 3028 31024 Toulouse Cedex 3
Inserm University of Toulouse Université Toulouse III - Paul Sabatier