Responsiveness of T Cells to Interleukin‐7 Is Associated with Higher CD4+T Cell Counts in HIV‐1–Positive Individuals with Highly Active Antiretroviral Therapy–Induced Viral Load Suppression

Abstract

Background. Despite suppression of the human immunodeficiency virus type 1 (HIV‐1) load by highly active antiretroviral therapy (HAART), recovery of CD4⁺ T cell counts can be impaired. We investigated whether this impairment may be associated with hyporesponsiveness of T cells to γ‐chain (γc) cytokines known to influence T cell homeostasis. Methods. The responsiveness of T cells to interleukin (IL)–2, IL‐7, and IL‐15 was determined by assessing cytokine‐induced phosphorylation of the signal transducer and activator of transcription 5 (STAT5) in peripheral T cells obtained from 118 HIV‐positive subjects and 13 HIV‐negative subjects. Results. The responsiveness of T cells to interleukin (IL)–7 but not to IL‐2 or IL‐15 was lower among HIV‐positive subjects than among HIV‐negative subjects. Among subjects with viral load suppression, the degree of IL‐7 responsiveness (1) correlated with naive CD4⁺ T cell counts and was a better immune correlate of the prevailing CD4⁺ T cell count than were levels of human leukocyte antigen–DR1 or programmed death–1, which are predictors of T cell homeostasis during HIV infection; and (2) was greater in subjects with complete (i.e., attainment of ⩾500 CD4⁺ T cells/mm³ ⩾5 years after initiation of HAART) versus incomplete immunologic responses. The correlation between plasma levels of IL‐7 and CD4⁺ T cell counts during HAART was maximal in subjects with increased IL‐7 responsiveness. Conclusions. Responsiveness of T cells to IL‐7 is associated with higher CD4⁺ T cell counts during HAART and thus may be a determinant of the extent of immune reconstitution.