CD8⁺ T cells in HIV disease exhibit cytokine receptor perturbation and poor T cell receptor activation but are responsive to γ-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)-2Rβ, common γ (Cγ) chain, IL-7Rα, IL-I5Rα; 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-7Rα in the central memory and effector memory subsets and of the Cγ chain in all maturation subsets of CD8⁺ T cells. IL- 7Rα⁺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 γ-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.