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Blood, 18 June 2009, Vol. 113, No. 25, pp. 6351-6360. Prepublished online as a Blood First Edition Paper on April 23, 2009; DOI 10.1182/blood-2009-02-206557. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2009-02-206557v1 113/25/6351    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Almeida, J. R. Articles by Appay, V. PubMed PubMed Citation Articles by Almeida, J. R. Articles by Appay, V. Related Collections Immunobiology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity Jorge R. Almeida1, Delphine Sauce1, David A. Price2,3, Laura Papagno1, So Youn Shin4, Arnaud Moris5, Martin Larsen1, Gianfranco Pancino4, Daniel C. Douek2, Brigitte Autran1, Asier Sáez-Cirión4, and Victor Appay1 1 Cellular Immunology Laboratory, Institut National de la Santé et de la Recherche Médicale Unité 945, Avenir Group, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie-Paris6, Paris, France; 2 Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; 3 Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff, United Kingdom; and 4 Unité de Régulation des Infections Rétrovirales and 5 Unité Virus et Immunité, Institut Pasteur, Paris, France CD8+ T cells are major players in the immune response against HIV. However, recent failures in the development of T cell–based vaccines against HIV-1 have emphasized the need to reassess our basic knowledge of T cell–mediated efficacy. CD8+ T cells from HIV-1–infected patients with slow disease progression exhibit potent polyfunctionality and HIV-suppressive activity, yet the factors that unify these properties are incompletely understood. We performed a detailed study of the interplay between T-cell functional attributes using a bank of HIV-specific CD8+ T-cell clones isolated in vitro; this approach enabled us to overcome inherent difficulties related to the in vivo heterogeneity of T-cell populations and address the underlying determinants that synthesize the qualities required for antiviral efficacy. Conclusions were supported by ex vivo analysis of HIV-specific CD8+ T cells from infected donors. We report that attributes of CD8+ T-cell efficacy against HIV are linked at the level of antigen sensitivity. Highly sensitive CD8+ T cells display polyfunctional profiles and potent HIV-suppressive activity. These data provide new insights into the mechanisms underlying CD8+ T-cell efficacy against HIV, and indicate that vaccine strategies should focus on the induction of HIV-specific T cells with high levels of antigen sensitivity to elicit potent antiviral efficacy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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