Background and objective The role of CD8+ T cells in autoimmune disease is poorly understood and may depend on the phase of disease. CD8+ T cells can contribute to autoimmunity by driving inflammation through cytokine release, tissue infiltration and cytotoxic T cell (CTL) function or by dampening the immune response through CD8+ regulatory T cells. To provide more insight into the role of CD8+ T cells during the development of autoimmune disease, we investigated the phenotype and function of CD8+ T cells in lymphoid tissue and peripheral blood during the earliest phases of rheumatoid arthritis (RA).
Methods We collected inguinal lymph node biopsies and peripheral blood from 20 individuals with arthralgia but without arthritis, who were positive for IgM rheumatoid factor (IgM-RF) and/or anti-citrullinated protein antibodies (ACPA; RA-risk individuals); 17 early RA patients; and 19 healthy controls (HCs). CD8+ T cell function and phenotype were analysed using flow cytometry. To measure cytokine production cells were stimulated for four hours with PMA/Ionomycin in the presence of Brefeldin A and Golgi stop.
Results We found higher frequencies of lymphoid memory CD8+CD45RO+ T cells in RA-risk individuals (p < 0.05) and early RA patients (p < 0.05) compared with HCs. In addition, we found higher frequencies of activated lymphoid CD8+CD45RA+CD69+ T cells in early RA patients compared with HCs (p < 0.05). Interleukin-(IL-)10 and interferon gamma (IFNg) production in lymphoid CD8+ T cells was decreased in the RA risk individuals compared with HCs (p < 0.01). There was a decrease in both IFNg and IL-17A production in lymphoid CD8+ T cells in early RA patients (p < 0.05). We did not detect changes in frequencies of cytotoxic effector CD8+ T cells in peripheral blood or lymphoid tissue during the earliest phases of RA. In lymphoid tissue of early RA patients there was a negative correlation between the CD8+IL-17A+ mean fluorescent intensity (MFI) and disease activity score in 28 joints (DAS28) (p = 0.005, r = -0.81) and swollen joint count 28 (SJC28; p = 0.01, r = -0.76) and between CD8+IL-10+MFI and DAS28 (p = 0.05, r = -0.67) and tender joint count 28 (TJC28; p = 0.02, r = -0.73). These data indicate that a decrease in lymphoid tissue derived regulatory and pro-inflammatory cytokines was related to disease activity.
Conclusion The data present here suggest that CD8+ T cells exhibit an exhaustive phenotype during the RA-risk phase and earliest phases of RA, which might be explained by continuous antigen presentation and CD8+ T cell activation.