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Clinical and Vaccine Immunology, January 2007, p. 74-80, Vol. 14, No. 1
1071-412X/07/$08.00+0 doi:10.1128/CVI.00250-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Nancy C. Connolly,2
William G. Buchanan,1 and
Charles R. Rinaldo Jr.1,3*
Department of Infectious Diseases and Microbiology, Graduate School of Public Health,1 Departments of Medicine,2 Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 152613
Received 8 July 2006/ Returned for modification 16 August 2006/ Accepted 23 October 2006
The failure of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells to control chronic HIV-1 infection could be due to the progressive loss of their capacities to undergo normal memory effector differentiation. We characterized and compared the expressions of CD27, CD28, CD57, and CD62L by Epstein-Barr virus (EBV)-, cytomegalovirus (CMV)-, and HIV-1-specific CD8+ T cells by six-color, eight-parameter flow cytometry. In contrast to the maturation of EBV- and CMV-specific memory CD8+ T cells, we found that HIV-1-specific CD8+ T cells did not display coordinated down-regulation of CD27 and up-regulation of CD57 and accumulated in an atypical CD27high CD57low subset. Moreover, the accumulation of CD27high CD57low HIV-1-specific CD8+ T cells was positively correlated with HIV-1 plasma viremia. The differentiation of HIV-1-specific CD8+ T cells to an effector subset is therefore impaired during chronic HIV-1 infection. This lack of normal CD8+ T-cell differentiation could contribute to the failure of cellular immune control of HIV-1 infection.
Published ahead of print on 1 November 2006.
Present address: Department of Medicine, Division of Infectious Diseases, University of California-Los Angeles, Los Angeles, CA 90095.
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