Both autoimmune processes and infectious agents have been implicated in the pathogenesis of multiple sclerois (MS). It is commonly assumed that activated T cells, which recognize antigens expressed in the CNS, enter the brain and initiate the inflammatory lesion. An additional characteristic feature of MS is the intrathecal production of oligoclonal immunoglobulins. We are studying both T- cell and B- cell autoimmune mechanisms in MS patients. Autoreactive T-cell clones specific for different brain proteins are established from blood and characterized with respect to their epitope specificity, MHC-restriction, TCR-usage, cytokine profile and functional cooperation with autoreactive B cells.
Recently developed treatments of MS include IFN-beta and Copaxone. The basis for the beneficial effect of these new agents is largely unknown. Our recent studies of the immunomodulatory effects of Copaxone revealed that this substance induces a cytokine shift towards a Th2 phenotype. This was seen with T-cell clones and also with peripheral blood cells, using ELISPOT assays.
In order to obtain further insight into the mutual interactions between the immune system and the nervous system, we are studying the production of neurotrophic factors by T cells, B cells and macrophages, which are present in MS-lesions.