Functional and phenotypic characterization of CD57+ CD4+ T cells and their association with HIV-1-induced T cell dysfunction

BE Palmer, N Blyveis, AP Fontenot… - The Journal of …, 2005 - journals.aai.org
The Journal of Immunology, 2005journals.aai.org
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-γ-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 …
Abstract
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-γ-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-γ 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.
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