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

Background. Despite suppression of the human immunodeficiencyvirus 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 maybe 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 (STATS) 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/mm ³ ≥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 maybe a determinant of the extent of immune reconstitution.