The CD8+HLA-DR+ T cells expanded in HIV-1 infection are qualitatively identical to those from healthy controls

被引:20
作者
Imamichi, Hiromi [1 ]
Lempicki, Richard A. [2 ]
Adelsberger, Joseph W. [2 ]
Hasley, Rebecca B. [1 ]
Rosenberg, Alice [3 ]
Roby, Gregg [1 ]
Rehm, Catherine A. [1 ]
Nelson, Amy [1 ]
Krishnan, Sonya [3 ]
Pavlick, Mark [1 ]
Woods, Christian J. [4 ]
Baseler, Michael W. [2 ]
Lane, H. Clifford [1 ]
机构
[1] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD USA
[2] SAIC Frederick Inc, Clin Serv Program, Appl Dev Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA
[3] SAIC Frederick Inc, Clin Monitoring Res Program, Clin Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA
[4] Washington Hosp Ctr, Washington, DC 20010 USA
基金
美国国家卫生研究院;
关键词
Activated CD8+T cells; Cell cycle; HIV; HLA-DR; Immune activation; HUMAN-IMMUNODEFICIENCY-VIRUS; HLA-DR; ACTIVATION ANTIGENS; IMMUNE ACTIVATION; EXPRESSION; LYMPHOCYTES; PHENOTYPE; DISEASE; MORTALITY; APOPTOSIS;
D O I
10.1002/eji.201142046
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2608 / 2620
页数:13
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