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

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-7R alpha 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-7R alpha expression, failed to induce T cell exhaustion, and primed Tcells. Persistent antigen also suppressed IL-7R alpha 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.