Proinflammatory CD20 + T cells contribute to CNS-directed autoimmunity
| Autor: | 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 |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Science Translational Medicine. 14 |
| ISSN: | 1946-6242 1946-6234 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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