CD161-positive CD4 T Cells in Rheumatoid Joint

Background: Activation of T cells participates in the pathogenesis of rheumatoid arthritis (RA) as demonstrated by effective clinical responses to abatacept treatment. Recent studies determine the significance of CD161 expression on CD4+T cells as the effector and regulator in autoimmunity; however, the implication of CD161+CD4+ T lymphocytes in RA remains to be fully defined. Methods: Expression of CD161 was examined in circulating lymphocytes in 140 RA patients and 140 age-and sex-matched healthy controls, and analyzed in paired peripheral blood and synovial fluid samples from 18 late-stage RA patients with further functional characterization of synovial CD161+CD4+ T cells. Results: There were no differences in circulating frequencies of CD161+ T cells and expression levels of CD161 in different T cell subsets. Increased CD161 expression levels were found in synovial T cells, especially in the CD4 subset. Functional analysis of synovial CD161+CD4+ T cells revealed significant intracellular IFN-γ expression upon PMA/ionomycin activation and cytotoxicity against target cells with IL-15 stimulation. Conclusions: Synovial CD161+CD4+ T cells with pro-inflammatory features like IFN-γ production and cytotoxicity ability might participate in the RA pathogenesis