Aberrant pro-inflammatory responses of CD20+ T cells in experimental arthritis

Abstract

CD20⁺ T cells comprise a highly inflammatory subset implicated in autoimmunity, including rheumatoid arthritis (RA). We sought to characterize the CD20⁺ T cell subset in the 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, produce increased levels of pro-inflammatory cytokines and are less susceptible to regulation by regulatory T cells. Notably, CD3⁺CD4⁺CD20⁺ and CD3⁺CD8⁺CD20⁺ T cells are enriched with CXCR5⁺PD-1⁺ T follicular helper cells and CXCR5^-PD-1⁺ peripheral T helper cells, subsets of T cells implicated in promoting B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues in RA. Our findings suggest CD20⁺ T cells are associated with inflammatory responses and may exacerbate pathology by promoting inflammatory B-cell responses.

Keywords: CD20(+) T cells; Collagen-induced arthritis (CIA); Regulatory T cells (Tregs); T follicular helper cells (Tfh); peripheral T helper cells (Tph).