The CD8+ HLA-DR+ T cells expanded in HIV-1 infection are qualitatively identical to those from healthy controls.
Citation: European Journal of Immunology. 42(10):2608-20, 2012 Oct.PMID: 22777759Institution: MedStar Washington Hospital CenterDepartment: Medicine/Pulmonary-Critical CareForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., ExtramuralSubject headings: *CD8-Positive T-Lymphocytes/im [Immunology] | *HIV Infections/im [Immunology] | *HIV-1/im [Immunology] | *HLA-DR Antigens/me [Metabolism] | *T-Lymphocyte Subsets/im [Immunology] | Adult | Biological Markers/me [Metabolism] | CD8-Positive T-Lymphocytes/vi [Virology] | Cell Cycle | Cell Cycle Proteins/ge [Genetics] | Cell Cycle Proteins/me [Metabolism] | Cell Proliferation | Cells, Cultured | Clonal Anergy | Gene Expression Regulation/im [Immunology] | Humans | Lymphocyte Activation | Middle Aged | Receptors, Antigen, T-Cell/im [Immunology] | T-Lymphocyte Subsets/vi [Virology]Year: 2012ISSN:- 0014-2980
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Journal Article | MedStar Authors Catalog | Article | 22777759 | Available | 22777759 |
HIV-induced immune activation leads to expansion of a subset of human CD8(+) T cells expressing HLA-DR antigens. Expansion of CD8(+) HLA-DR(+) T cells can be also observed in non-HIV settings including several autoimmune diseases and aging. Although these cells are felt to represent "immune exhaustion" and/or to be anergic, their precise role in host defense has remained unclear. Here, we report that this subset of cells exhibits a restricted repertoire, shows evidence of multiple rounds of division, but lacks markers of recent TCR engagement. Detailed cell cycle analysis revealed that compared with their CD8(+) HLA-DR(-) counterpart, the CD8(+) HLA-DR(+) T-cell pool contained an increased fraction of cells in S-phase with elevated levels of the G2/M regulators: cyclin A2, CDC25C, Cdc2 (CDK1), indicating that these cells are not truly anergic but rather experiencing proliferation in vivo. Together, these data support a hypothesis that antigen stimulation leads to the initial expansion of a CD8(+) pool of cells in vivo that undergo further expansion independent of ongoing TCR engagement. No qualitative differences were noted between CD8(+) HLA-DR(+) cells from HIV(+) and HIV(-) donors, indicating that the generation of CD8(+) HLA-DR(+) T cells is a part of normal immune regulation that is exaggerated in the setting of HIV-1 infection. 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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