Characterization of CD8⁺ T lymphocytes in multiple sclerosis and study of their potential involvement in the mechanism of molecular mimicry.

Renaud DU PASQUIER, Samantha JILEK TERRASSE (to March 2012), Emilie JAQUIERY (to February 2010), Sonia NEGRO (to February 2011), Guillaume PERRIARD (from May 2011), Samanta SIMIONI, Mathieu CANALES, Laurence GUIGNARD (to July 2008) and Andreas LYSANDROPOULOS (to September 2009)

Multiple sclerosis (MS) is the most common human demyelinating disease of the central nervous system (CNS). Yet, the cause of MS still eludes researchers. Recent data suggest that CD8⁺ T cells might play a more important role in MS than previously thought, particularly in the early steps of this disease. We know that CD8⁺ T cells constitute a crucial anti-viral line of defense. We also know that there are strong epidemiological elements speaking for a viral etiology of MS. One of the leading hypotheses is that within a genetically susceptible host immune system, virus-derived epitopes presenting T cells could activate self-reactive T cells. This antigen cross-recognition is known as “molecular mimicry”. In this project, we want to examine in detail the relationship between viruses and CD8⁺ T cells in MS patients.

1) We are currently studying the cellular immune profile of CD8⁺ T cells in the blood and the cerebrospinal fluid (CSF) of patients with a first episode consistent with MS by flow cytometry. 2) With the ELISPOT assay, we are characterizing the CD4⁺ and CD8⁺ T cell responses specific for different myelin protein in patients within different categories of MS patients. 3) Using ex vivo cytotoxic assays, we will evaluate the T cell-mediated cross-reactivity between selected viruses and myelin epitope-derived peptides. 4) In the future, using the tetramer technology, we aim to precisely characterize self-reactive myelin_epitopes- specific and viruses_epitope- specific CD8⁺ T cells in the blood and the cerebrospinal fluid of patients with a first episode consistent with MS.

Dernière modification le 26.03.2012 - Impressum - Informations juridiques