title: Interleukin-7 receptor signaling is deficient in CD4+ T cells from HIV-infected persons and is inversely associated with aging.
abstract: 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.
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, and University Hospitals, Cleveland, Ohio 44106, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bazdar
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kalinowska
authors.forename: Scott F
authors.initials: SF
authors.lastname: Sieg
mesh_terms: D000375:Aging / Q000502:physiology*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor