Inverse correlation between IL‐7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation

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Abstract
Persistence is a hallmark of infection by viruses such as HIV, hepatitis B virus, hepatitis C virus and LCMV. In the case of LCMV, persistence may often be associated with exhaustion of CD8+ T cells. We demonstrate here that persistent antigen suppressed IL‐7Rα expression and this correlated with T cell exhaustion and reduced expression of the anti‐apoptotic molecule B cell leukemia/lymphoma 2 (Bcl‐2). In contrast, exposure to short‐lived antigen only temporarily suppressed IL‐7Rα expression, failed to induce T cell exhaustion, and primed T cells. Persistent antigen also suppressed IL‐7Rα expression on primed T cells and this correlated with exhaustion of a previously stable primed T cell population. These findings suggest that antigen longevity regulates T cell fate.