CD8+ T cells in HIV disease exhibit cytokine receptor perturbation and poor T cell receptor activation but are responsive to gamma-chain cytokine-driven proliferation.

BACKGROUND: Cytokines are important for inducing T cell maturation, proliferation, and survival. Despite the known dysregulation of cytokines in human immunodeficiency virus (HIV) infection, cytokine receptor expression is relatively unexplored.

METHODS: We examined maturation markers (naive, central memory, effector memory, and effector); the cytokine receptors interleukin (IL)-2R beta , common gamma (C gamma ) chain, IL-7R alpha , IL-15R alpha; and proliferative responses of T cells in a cohort of HIV-infected pediatric patients (median age, 14.82 years) receiving antiretroviral therapy, arbitrarily designated as immunologic responders (group I) and nonresponders (group II) on the basis of a CD4+ T cell count cutoff of 25%.

RESULTS: Patients had increased percentages of effector memory CD8+ T cells, in comparison with those in healthy control subjects, with reduced expression of IL-7R alpha in the central memory and effector memory subsets and of the C gamma chain in all maturation subsets of CD8+ T cells. IL-7R alpha +CD8+ T cell percentages were directly correlated with CD4+ T cell percentages. In immunologic nonresponders, anti-CD3+ or HIV Gag antigen-induced CD8+ T cell proliferation was impaired, but proliferation in response to the homeostatic cytokines IL-2 and IL-15 was preserved.Conclusions. Cytokine receptor deficiencies may contribute to immune deficiency in HIV-infected patients, and gamma -chain-utilizing cytokines may play an important role in vivo in maintaining the memory subsets of T cells in patients with CD4+ T cell deficiency.