CD20⁺ T cells are associated with inflammatory responses in experimental arthritis

Abstract

CD20⁺ T cells comprise a small but highly inflammatory subset that has been implicated in autoimmunity, including rheumatoid arthritis (RA). We sought to characterise the CD20⁺ T cell subset at the site of inflammation in murine collagen-induced arthritis (CIA) model of RA and investigate the phenotype and functional relevance of CD3⁺CD20⁺ T cells in the lymph nodes and arthritic joints using flow cytometry and immunohistochemistry. We demonstrate that CD3⁺CD4⁺CD20⁺ and CD3⁺CD8⁺CD20⁺ T cells are expanded in the draining lymph nodes of CIA mice. In addition, compared to naïve mice and those that did not develop clinical symptoms, CD20 expressing T cells of arthritic mice produced increased levels of pro-inflammatory cytokines (GM-CSF, TNF-a, IL-17, and INF-g). Notably, CD3⁺CD4⁺CD20⁺ and CD3⁺CD8⁺CD20⁺ T cells of disease mice were enriched with CXCR5⁺PD-1⁺ T follicular helper cells and CXCR5^-PD-1⁺ peripheral T helper cells, subsets of T cells that have been implicated in promoting B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues in RA. Importantly, CD3⁺CD20⁺ T cells were detected in the inflamed regions in the lymph nodes and paws of arthritic mice. Our findings suggest that CD20⁺ T cells are associated with inflammatory responses in the arthritic joint and may exacerbate pathology by promoting inflammatory B cell responses.