The CD8+HLA‐DR+ T cells expanded in HIV‐1 infection are qualitatively identical to those from healthy controls |
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Authors: | Hiromi Imamichi Richard A. Lempicki Joseph W. Adelsberger Rebecca B. Hasley Alice Rosenberg Gregg Roby Catherine A. Rehm Amy Nelson Sonya Krishnan Mark Pavlick Christian J. Woods Michael W. Baseler H. Clifford Lane |
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Affiliation: | 1. Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, , Bethesda, MD, USA;2. Clinical Services Program, Applied/Developmental Research Directorate, SAIC‐Frederick, Inc., Frederick National Laboratory for Cancer Research, , Frederick, MD, USA;3. Clinical Monitoring Research Program, Clinical Research Directorate, SAIC‐Frederick, Inc., Frederick National Laboratory for Cancer Research, , Frederick, MD, USA;4. Washington Hospital Center, , Washington, DC, USA |
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Abstract: | 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. |
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Keywords: | Activated CD8+ T cells Cell cycle HIV HLA‐DR Immune activation |
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