title: Impaired TCR-mediated induction of Ki67 by naive CD4+ T cells is only occasionally corrected by exogenous IL-2 in HIV-1 infection.
abstract: Perturbations in naive T cell homeostasis and function may play a major role in the immunodeficiency that accompanies HIV infection. By examining naive CD4(+) T cell function on a single cell basis, we provide evidence that these cells have significant qualitative defects in HIV disease. Ki67, a molecule expressed during cell cycle progression, is induced less efficiently among naive CD4(+) T cells from HIV-infected individuals following activation with anti-TCR Ab. The impairment in Ki67 expression is evident even when a separate function, CD62L down-modulation, is within normal ranges. Moreover, the defects in Ki67 induction are only sometimes corrected by the addition of rIL-2 to cell cultures. An initial assessment of IL-2 unresponsiveness in cells from selected HIV-infected individuals suggests that the defect is not a consequence of impaired IL-2R expression or IL-2R signaling capability. Qualitative defects in naive T cells that cannot be routinely corrected by IL-2 have significant implications for disease pathogenesis and for strategies using IL-2 as a vaccine adjuvant in HIV disease.
authors: Department of Medicine, Division of Infectious Diseases, Case Western Reserve University and University Hospitals of Cleveland, Center For AIDS Research, Cleveland, OH 44106, USA. sfs2@po.cwru.edu
authors: Scott F
authors: SF
authors: Sieg
authors: Douglas A
authors: DA
authors: Bazdar
authors: Michael M
authors: MM
authors: Lederman
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology*; D007399:Interphase / Q000276:immunology*; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D007376:Interleukin-2; D019394:Ki-67 Antigen; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D019041:L-Selectin