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Impaired Induction of CD27 and CD28 Predicts Naive CD4 T Cell Proliferation Defects in HIV Disease¹

Angel A. Luciano^*,, Michael M. Lederman^*, Alice Valentin-Torres, Douglas A. Bazdar^* and Scott F. Sieg^2,*

^* Case Western Reserve University and University Hospitals of Cleveland, Center for AIDS Research, Department of Medicine, Division of Infectious Diseases, Cleveland, Ohio 44106; Rainbow Babies and Children’s Hospital, Department of Pediatrics, Division of Neonatology, Cleveland, Ohio 44106; and Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio 44106

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by grants from the National Institutes of Health (AI38858, AI07024, and the Case/UH Center for AIDS Research, AI36219) and the William Randolph Hearst Neonatology Research Grant.

² Address correspondence and reprint requests to Dr. Scott F. Sieg, Case Western Reserve University, School of Medicine, BRB, Room 1020, 2109 Adelbert Road, Cleveland, Ohio 44106-4984. E-mail address: sfs2{at}case.edu

³ Abbreviations used in this paper: TREC, TCR excision circles.

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