Expression of γ‐chain cytokine receptors on CD8+ T cells in HIV infection with a focus on IL‐7Rα (CD127)

Abstract

When interleukin-2 (IL-2) receptor γ-chain (γ(C))-sharing cytokine receptors on T cells bind their specific ligands (IL-2, -4, -7, -9, -15 or -21), they initiate a variety of cell signals that promote survival, differentiation or antiviral or antitumor cytolytic functions. Although expression of the γ(C) is constitutive across T-cell subsets, the varying expression of other receptor complex components can regulate cytokine signalling and function. Impaired γ(C) cytokine activity in HIV infection, and the role of γ(C) cytokines in CD8(+) T-cell function and homeostasis, implicates these molecules among potential contributors to the observed decline of cytolytic activity (CTL) in HIV disease. In particular, this review will be highlighting information about the IL-7 receptor (IL-7R) complex, which is composed of the γ(C) and the IL-7Rα (CD127) chains. There has been an abundance of HIV-related CD127 research and its important role in CD8(+) T-cell survival and function. The expression of CD127 undergoes dramatic changes throughout the course of T-cell responses in HIV infection. The expression of CD127 is significantly decreased in progressive HIV disease, whereas effective antiretroviral therapy results in its recovery. Observations of impaired IL-7 activity in HIV(+) individuals have suggested that CD127 has an important role in HIV immunopathogenesis. In addition, a soluble form of CD127 (sCD127) is upregulated in the plasma of HIV(+) individuals. Hence, CD127 is being increasingly considered as a marker of disease prognosis, and related information may provide insight into understanding the expression and role of other γ(C) receptors in HIV disease and contribute to the development of novel cytokine-based therapeutics.