Human lymph-node CD8+ T cells display an altered phenotype during systemic autoimmunity

摘要

Although many studies are focused on auto-reactive CD4+ T cells, the precise role of CD8+ T cells in autoimmunity is poorly understood. The objective of this study is to provide more insight into the phenotype and function CD8+ T cells during the development of autoimmune disease by studying CD8+ T cells in human lymph-node biopsies and peripheral blood obtained during the earliest phases of rheumatoid arthritis (RA). Here, we show that lymphoid pro-inflammatory CD8+ T cells exhibit a less-responsive phenotype already during the earliest phases of autoimmunity compared with healthy individuals. We found an increase in CD8+ memory T cells in lymphoid tissue during the earliest phases of autoimmunity, even before clinical onset of RA, accompanied by an increased frequency of non-circulating or recently activated (CD69+) CD8+ T cells in lymphoid tissue and peripheral blood. Importantly, lymphoid pro-inflammatory CD8+IL-17A+ T cells displayed a decreased capacity of cytokine production, which was related to disease activity in early RA patients. In addition, a decreased frequency of regulatory CD8+IL-10+ T cells in peripheral blood was also related to disease activity in early RA patients. Our results suggest that different CD8+ T-cell subsets are affected already during the earliest phases of systemic autoimmunity.