CNS AUTOIMMUNITY · Mechanisms of antigen presentation in central nervous system autoimmune disease

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Project objective

Multiple sclerosis (MS) is a demyelinating inflammatory disease of the central nervous system (CNS) that is believed to result from the activation of auto-reactive T lymphocytes. Experimental autoimmune encephalitis (EAE) models of MS have been developed and demonstrate a role for CD4 T cells.However, current ideas about disease pathogenesis suggest a critical role for CNS antigen-specific CD8 T cells. I propose to establish a CD8 T cell mediated mouse model of EAE to address several critical unknowns: How does the immune system become exposed to CNS antigen (e.g. myelin basic protein, MBP)? What are the cellular and molecular determinants that result in T cell tolerance (the inactivation of T cells specific to CNS antigen) versus T cell activation (inflammatory responses that drive CNS autoimmunity)? Evidence suggests that the antigen presenting cells responsible for capturing and presenting CNS antigens may be dendritic cells (DCs). Based on clinical observations, I hypothesize that CD4 T cells serve as triggers causing auto-reactive CD8 T cells to become reactive instead of tolerant.The proposed studies differ from my previous research experiences in that they involve immunology and rely heavily on techniques specific to this field, whereas my former work has been primarily in biophysics and lipid chemistry. Training in the lab of a leader in DC immunology and cross-presentation at a world-renowned institution will provide me the skill set needed to advance my career interests and help me fulfil my desire to lead an independent group, combining my interests in CNS immunology and neuro-pharmacology.

Original text from CORDIS.

Participants

• INSTITUT PASTEUR · PARISCoordinatorFrance

Links

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