CD8+ T cells are critical for collagen induced arthritis disease progression (130.46)

Abstract

Abstract Despite extensive study of T cells in Rheumatoid Arthritis (RA), relatively little is known regarding the role of CD8+ T cells in RA progression. Here, we use the collagen induced arthritis (CIA) model, and deplete, prior to disease onset, CD8α+ T and dendritic cells (DCs) or CD8β+ T cells in collagen immunized DBA mice. Beginning 23 days post immunization, mice received repeated injections of 100μg anti-CD8α(53-6.7), or anti-CD8β(H35-17.2) or IgG2a isotype. Depletion of CD8αor CD8β cells did not affect the prevalence of disease; suggesting that CD8+ cells are not necessary for disease initiation (isotype=87%, anti-CD8α=78%,and anti-CD8β=78%, n=9/group). However, there was a significant reduction in arthritis duration with CD8α depletion (anti-CD8α= 4.9±2.0 vs. control= 8.6±1.1 arthritic days, p<0.01) and with CD8β depletion (anti-CD8β= 8.1±1.7 vs. control=13.5±1.9 arthritic days). Disease severity was also reduced in CD8α and CD8β depleted mice. Depleted mice had maximum mean paw scores of 2.4±1.1 (CD8α depleted) and 2.5±1.0 (CD8β depleted) compared to 4.5±1.8 in controls, p< 0.03. This was accompanied by reduced mononuclear cell infiltrate, pannus formation and joint destruction, as observed by H&E staining. We have shown that CD8+ T cells are necessary for CIA progression and are critical contributors to disease severity.