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Lack of Epstein-Barr virus- and HIV-specific CD27 CD8+ T cells is associated with progression to viral disease in HIV-infection

van Baarle, Debbiea,b,*; Kostense, Stefana,*; Hovenkamp, Egberta; Ogg, Grahamc; Nanlohy, Neninga; Callan, Margaret FCc; Dukers, Nicole HTMd; McMichael, Andrew Jc; van Oers, Marinus HJb; Miedema, Franka,e

AIDS:
Basic Science
Abstract

Objective: Despite readily detectable virus-specific CD8+ T cells in most HIV-infected patients, immune surveillance is eventually lost, leading to progression to AIDS. To investigate the underlying mechanism of this loss of immune control phenotypic analysis of HIV- and Epstein–Barr virus (EBV)-specific CD8+ T cells was performed.

Design: In three clinically distinct groups, long-term asymptomatics, progressors to opportunistic infections and progressors to EBV-associated non-Hodgkin lymphoma's (NHL), both number and phenotype of virus-specific CD8+ T cells was studied longitudinally.

Methods: The number of HIV- and EBV-specific T cells were determined using HLA-peptide tetrameric complexes. The phenotype of these virus-specific T cells was investigated by costaining with CD27 and CD45RO and thereby identifying specific subsets of CD8+ T cells.

Results: Individuals co-infected with HIV and EBV persistently had low numbers of HIV-specific CD27− T cells, in contrast to rising numbers of EBV-specific CD27− CD8+ T cells. However, HIV-infected individuals developing EBV-associated AIDS-related NHL had very low numbers of EBV-specific CD27− CD8+ T cells. Higher numbers of HIV-specific CD27− CD8+ T cells were associated with delayed disease progression. Virus-specific CD27− T cells, compared with CD27+ T cells showed elevated interferon-gamma production in response to viral peptides in vitro, indicative for strong effector function.

Conclusions: Taken together, our data indicate that virus-specific CD27− T cells may be important effector T cells in controlling chronic viral infections in humans and that lack of differentiation into CD27− effector T cells may lead to progression of viral disease.

Author Information

From the aDepartment of Clinical Viro-Immunology, CLB/Sanquin & Landsteiner Laboratory of the Academic Medical Center, University of Amsterdam, the bDepartment of Hematology, Academic Medical Center, Amsterdam, The Netherlands, the cMolecular Immunology Group, Institute of Molecular Medicine, Oxford, UK, the dDepartment of Public Health, Municipal Health Service, Amsterdam and the eDepartment of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Note: *These authors contributed equally to the presented work.

Correspondence to D van Baarle, Dept. Clinical Viro-Immunology, CLB, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands. Tel: +31 20 5123314; fax: +31 20 5123310; email: d_van_baarle@clb.nl

Received: 5 October 2001; revised: 24 May 2002; accepted: 10 June 2002.

© 2002 Lippincott Williams & Wilkins, Inc.