Interleukin-7 Receptor Signaling Is Deficient in CD4+ T Cells from HIV-Infected Persons and Is Inversely Associated with Aging

Loss of interleukin-7 (IL-2) receptor expression has been described in T lymphocytes from persons with human immunodeficiency virus (HIV) infection, potentially contributing to perturbations in T cell homeostasis. We investigated IL-7 receptor signaling by measuring signal transducer and activator of transcription 5 (STAT5) phosphorylation in CD4(+) T cell subsets from HIV-infected persons. We determined that CD45RA(-) memory cell subsets (both CD27(+) and CD27(-)) displayed the most robust immediate responses to IL-7, whereas naive CD4(+) T cells sustained the signal most efficiently. Memory CD4(+)T cells with a terminal phenotype (CD45RA(+)CD27(-)) responded poorly to IL-7 stimulation. Defects in signaling were observed in cells from viremic HIV-infected persons and were especially pronounced in CD45RA(-)CD27(-) memory subset. Although CD127 expression was diminished for T cells from HIV-infected persons, it was not directly related to IL-7 receptor signaling function. Instead, age was inversely related to IL-7 signaling in cells from both HIV-infected viremic subjects and healthy control subjects. Thus, HIV infection results in impaired IL-7 responsiveness, especially in memory CD4(+) T cells, and this defect is likely compounded by aging.