Disruption of the gamma c cytokine network in T cells during HIV infection.

ABSTRACT

The common gamma chain (gammac)-sharing cytokines (IL's-2, 4, 7, 9, 15, and 21) play a vital role in the survival, proliferation, differentiation and function of T lymphocytes. As such, disruption of their signaling pathways would be expected to have severe consequences on the integrity of the immune system. Indeed, it appears that the signaling network of these cytokines is both disrupted and exploited by HIV at various stages of infection. IL-2 secretion and signaling downstream of its receptor are impaired in T cells from chronically-infected HIV+ patients. Elevated plasma IL-7 levels and decreased IL-7Ralpha expression in patient T cells results in significantly decreased responsiveness to this critical cytokine. Interestingly, IL-2 and IL-15 are also able to render CD4+ T cells permissive to HIV infection through their influence on the activity of the APOBEC3G deaminase enzyme. Herein, we describe the current state of knowledge on how the gammac cytokine network is affected during HIV infection, with a focus on how this impairs CD4+ and CD8+ T cell function while also benefiting the virus itself. We also address the use of cytokines as adjuncts to highly active antiretroviral therapy to bolster immune reconstitution in infected patients.