Impaired induction of CD27 and CD28 predicts naive CD4 T cell proliferation defects in HIV disease.
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.
Luciano
Angel A
AA
Case Western Reserve University and University Hospitals of Cleveland, Center for AIDS Research, Department of Medicine, Division of Infectious Diseases, Cleveland, Ohio 44106, USA.
Lederman
Michael M
MM
Valentin-Torres
Alice
A
Bazdar
Douglas A
DA
Sieg
Scott F
SF
D015415:Biomarkers / Q000378:metabolism; D018106:CD28 Antigens / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism*; D011237:Predictive Value of Tests; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology