Abstract
Many immunological defects have been described in HIV disease, including a diminished capacity of naive CD4+ T cells to expand after TCR stimulation. The mechanisms underlying impaired naive CD4+ T cell expansion in HIV disease are not well described. Using a rigorous phenotypic definition of naive T cells, we found that cell cycle entry after TCR engagement was restricted to cells that increased surface expression of costimulatory molecules CD27 and CD28. Induction of these receptors, however, was not sufficient to result in cell cycle entry among the CD4+CD31- naive T cell subset. Analyses of cells from HIV-infected persons indicated that naive CD4+CD31+ T cells from these subjects were impaired in their ability to enter the cell cycle after stimulation and this impairment was predicted by the relatively poor induction of costimulatory molecules on these cells. Thus, failure to increase surface expression of costimulatory molecules may contribute to the naive T cell expansion failure that characterizes HIV infection.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Biomarkers / metabolism
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CD28 Antigens / biosynthesis
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CD28 Antigens / metabolism*
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CD28 Antigens / physiology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism*
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CD4-Positive T-Lymphocytes / pathology
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Cell Cycle / immunology
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Cell Membrane / pathology
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Cell Proliferation*
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HIV Infections / immunology*
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HIV Infections / metabolism
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HIV Infections / pathology*
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Humans
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Immunophenotyping
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Platelet Endothelial Cell Adhesion Molecule-1 / biosynthesis
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Platelet Endothelial Cell Adhesion Molecule-1 / metabolism*
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Predictive Value of Tests
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism
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Resting Phase, Cell Cycle / immunology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / pathology
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / antagonists & inhibitors*
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / biosynthesis
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / physiology
Substances
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Biomarkers
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CD28 Antigens
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Platelet Endothelial Cell Adhesion Molecule-1
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Receptors, Antigen, T-Cell
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Tumor Necrosis Factor Receptor Superfamily, Member 7