Grant: Operating Grant

Impaired cytotoxic T-cell (CTL) activity and altered thymic function likely contribute to progression of HIV disease but the reasons for this remain to be established. Interleukin (IL)-7 signaling is essential for both CTL and thymic function and recent findings in our laboratory implicate a role for the regulation of the IL-7 receptor alpha (CD127) in the immunopathogenesis of HIV infection. We have shown that a soluble form of CD127 (sCD127) is released by CD8+ T-cells and demonstrated that sCD127 can inhibit IL-7 activity in vitro. In addition, we have detected sCD127 in human plasma and found that it is increased in HIV infection. The proposed work will investigate the mechanism(s) by which sCD127 is released by CD8+ T-cells and thymocytes and its role in HIV infection in vitro. Lastly, we will examine the effects of IL-7 therapy on the expression of sCD127 in SIV infection of rhesus macaques (an established model of HIV infection) as well as in effectively-treated HIV+ adults. Regulation and/or function of sCD127 may be important in explaining HIV-associated immune dysfunction and may lead to the development of novel immune-based therapies. Soluble CD127 has the potential to be clinically useful, both as an indicator of disease activity but, more importantly, as an immunotherapeutic agent.