The role of CD4+ and CD8+ T cells in the Evolution of SCW Induced Arthritis and in Oral Tolerance
Cook, Melissa A.
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Injection of Group A streptococcal cell wall (SCW) peptidoglycan-polysaccharide complexes in susceptible rats induces acute inflammation in the joints followed by chronic arthritis, producing an attractive animal model for rheumatoid arthritis. Infiltration of neutrophils into the synovium characterizes the acute phase while accumulation of T cells and monocytes mediates the chronic phase. In this study, we first investigated the role of CD4+ and CD8+ T cells in the evolution of SCW-induced arthritis by in vivo immuno-deletion of these cells. We found that neither CD4+ nor CD8+ T cells affected acute inflammation. In contrast, both CD4 + and CD8+ T cells, at least in part, regulated the chronic response. Unexpectedly, CD8+ T cells played a more important role in the chronic phase because their deletion caused a dramatic increase in IL-4, an anti-inflammatory cytokine. Importantly, oral administration of SCW is known to suppress SCW induced arthritis in a dose dependent manner, however, the cells involved in oral tolerance are ill defined. As our second objective, we assessed the same in vivo immuno-deletion of CD4+ and CD8+ T cells. In orally tolerized animals, both CD4+ and CD8+ immuno-deletion resulted in an increase in the acute response, but only a partially resolved chronic inflammation. Immunohistochemical staining revealed that TGF-~, an anti-inflammatory cytokine, was markedly increased in the orally tolerized gut tissue, but not in the control animals. CD4+ and CD8+ immuno-deletion reduced the amount of TGF-𝛽 in the gut, compared to the tolerized animals. Therefore, our results demonstrated that both CD4+ and CD8+ T cells play an inhibitory role in acute inflammation in oral tolerance. In chronic inflammation, however, other factors may be important in helping CD4+ or CD8+ T cells maintain tolerance.With honors.