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The Journal of Immunology, 2006, 177: 5145-5154.
Copyright © 2006 by The American Association of Immunologists, Inc.

High Cytotoxic and Specific Migratory Potencies of Senescent CD8+CD57+ Cells in HIV-Infected and Uninfected Individuals1

Yannick Le Priol*, Denis Puthier{dagger}, Cédric Lécureuil*, Christophe Combadière*, Patrice Debré*, Catherine Nguyen{dagger} and Béhazine Combadière2,*

* Institut National de la Santé et de la Recherche Médicale Unité 543, Université Pierre et Marie Curie Paris 6, Hôpital Pitié-Salpêtrière, Paris, France; and {dagger} Institut National de la Santé et de la Recherche Médicale ERM206/TAGC, Université d’Aix-Marseille II, Parc Scientifique de Luminy, Marseille, France

CD8+CD57+ T lymphocytes, present at low levels in the peripheral blood of healthy individuals expand during HIV infection and remain elevated during chronic infection. Their role in the immune response remains unclear. We performed a large-scale gene array analysis (3158 genes) to characterize them and, interestingly, found no distinction in the transcriptional profiles of CD8+CD57+ T lymphocytes from HIV-infected and uninfected subjects. In both groups, these cells showed specificity for multiple Ags and produced large amounts of IFN-{gamma} and TNF-{alpha}. The transcriptional profiles of CD8+CD57+ and CD8+CD57 cells, however, differed substantially. We propose that CD8+CD57+ cells were Ag-driven effector cells with very high cytotoxic effector potential including perforin, granzymes, and granulysin, regardless of HIV status. At both the messenger and protein levels, they expressed more adhesion molecules and fewer chemokine receptors (CCR7 and CXCR4) than CD8+CD57 cells but expressed preferentially CX3CR1. The lower expression level of genes involved in cell cycle regulation showed limited proliferation capacities of CD8+CD57+ even in response to TCR and IL-2, IL-7, and IL-15 stimulation. CD8+CD57+ T cells from both HIV and uninfected subjects maintain effective cytotoxic potentials but are destined to migrate to nonlymphoid tissues without further cycling.

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 by Agence Nationale de Recherches sur le Syndrome d’immunodéficience acquise (SIDA) Y.L.P. was a recipient of a fellowship from the Agence Nationale de Recherche sur le SIDA.

2 Address correspondence and reprint requests to Dr. Béhazine Combadière, Université Pierre et Marie Curie Paris 6, 91 bd de l’hôpital, 75013 Paris, France. E-mail address: combadie{at}ccr.jussieu.fr

3 Abbreviations used in this paper: UI, uninfected; FC, fold change; DC, dendritic cell; SNARF, seminaphthorhodafluor; p-c-jun, phosphorylated c-jun.




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