Functional and phenotypic characterization of CD57+CD4+ T cells and their association with HIV-1-induced T cell dysfunction.
HIV-1 replication is associated with reduced or absent HIV-1-specific CD4+ T cell proliferation and skewing of HIV-1-specific CD4+ T cells toward an IFN-gamma-producing, CCR7- phenotype. The CCR7- T cell population is heterogeneous and can be subdivided based on the expression of CD57. Although CD57 expression on CD8+ T cells is associated with proliferation incompetence and replicative senescence, less is known about the function of CD57-expressing CD4+ T cells. In this study, the frequency, phenotype, and function of CD57+CD4+ T cells were evaluated in 25 HIV-1-infected subjects and 10 seronegative controls. CD57+CD4+ T cells were found to be proliferation incompetent, even after strong mitogen stimulation. Percentages of CD4+ T cells that expressed CD57 were significantly higher in untreated HIV-1-infected subjects than in HIV-1-seronegative donors, and CD57 expression did not normalize in subjects receiving at least 6 mo of effective antiretroviral therapy. CD57 was predominately expressed on the CCR7- fraction of the CD4+ T cell compartment and accounted for the majority of cells in the CCR7-CD45RA+ population from untreated HIV-1-infected subjects. HIV-1-specific CD4+ T cells producing only IFN-gamma had the highest expression of CD57, whereas few cells producing IL-2 alone expressed CD57. These findings further define a novel population of proliferation-incompetent CD4+ T cells that are generated in the presence of chronic Ag exposure. A better understanding of the generation and persistence of CD57+ T cells in HIV-1 infection could provide important insights into the immunopathogenesis of this disease.
Palmer
Brent E
BE
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Blyveis
Naomi
N
Fontenot
Andrew P
AP
Wilson
Cara C
CC
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D018959:CD57 Antigens / Q000032:analysis*; D016022:Case-Control Studies; D049109:Cell Proliferation; D015658:HIV Infections / Q000209:etiology / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis; D037182:T-Cell Antigen Receptor Specificity
C515370:CCR7 protein, human; D018959:CD57 Antigens; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens