Proinflammatory CD20 <sup>+</sup> T cells contribute to CNS-directed autoimmunity
Jasmin Ochs, Nitzan Nissimov, Sebastian Torke, Marie Freier, Katja Grondey, Julian Koch, Matthias Klein, Linda Feldmann, Cathrin Gudd, Tobias Bopp, Silke Häusser‐Kinzel, Martin S. Weber
Abstract
The origin and function of CD20 + T cells are poorly understood. Here, we characterized CD20 + T cells in mice and humans and investigated how they are affected by anti-CD20 antibody treatment. We report that murine CD20 + T cells are unable to endogenously express the B cell lineage marker CD20; the development of CD20 + T cells in rodents requires the presence of CD20-expressing B cells. Our results demonstrated that both murine and human T cells acquire CD20 from B cells via trogocytosis while being activated by an antigen-presenting B cell. In patients with multiple sclerosis (MS) and mice with experimental autoimmune encephalomyelitis (EAE), expression of CD20 on T cells is associated with an up-regulation of activation markers, proinflammatory cytokines, and adhesion molecules, suggesting high pathogenic potential. Supporting this hypothesis, CD20 + T cells expand during active EAE in rodents; furthermore, adoptive transfer of CD20 + T cells into EAE-diseased mice worsened histological and clinical severity. Of direct therapeutic relevance, we demonstrate that the exclusive therapeutic elimination of CD20 + T cells effectively ameliorates EAE, independent of B cells. The results support the hypothesis that CD20 + T cells arise upon B cell–T cell interaction and that depletion of CD20 + T cells might contribute to the success of anti-CD20 antibody therapies in MS and other inflammatory disorders.