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 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 gamma-chain (gamma c) 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/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 may be a determinant of the extent of immune reconstitution.