011 – The role of CD20+ T cells in induced and spontaneous EAE models
Jasmin Ochs (1) – Silke Husser-Kinzel (1) – Wolfgang Brck (1) – Martin S. Weber (1, 2)
Department of Neuropathology, University medical center, Georg-August University Gttingen (1) – Department of Neurology, University medical center, Georg-August University Gttingen (2)
Multiple Sclerosis (MS) is one of the most prevalent disabling neurological diseases of young adults. MS patients develop lesions, consisting of infiltrating immune cells such as T cells, B cells and monocytes with areas of demyelination, within the central nervous system. Autoimmune T cells, as well as self-antigen presenting B cells, are strongly suggested to play an important role in the development and progression of MS. New therapies with anti-CD20 antibodies (e.g. rituximab, ocrelizumab) showed promising effects on MS propagation in patients via the depletion of CD20+ B cells. However, CD20dim expressing T cells were discovered and are accordingly newly investigated as a potential alternative therapeutic target of anti-CD20 antibody treatment. The functional properties of these CD20+ T cells are not yet known. Based on the following findings, we hypothesize that the depletion of CD20+ T cells may contribute to the positive therapeutic effects of anti-CD20 treatment. Firstly, CD20+ T cells were shown to be increased in MS patients compared to healthy controls. CD20+ T cells also exhibited a more pro-inflammatory phenotype compared to CD20- T cells (higher percentage of GM-CSF+, IL-17+, IL-4+, IL-2+ and IFNg+ cells). Treatment by anti-CD20 antibody therapy led to a depletion of CD20+ T cells, which were able to replete after treatment stop. To date, there is no data on the functional relevance of CD20+ T cells and their role in the clinical effectiveness of anti-CD20 treatment. To analyze CD20+ T cells and their possible therapeutic function we will employ different EAE (experimental autoimmune encephalomyelitis) mouse models as well as different genetically modified mouse models.