Proinflammatory CD20⁺ T cells contribute to CNS-directed autoimmunity.

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.