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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2238-2247. Prepublished online as a Blood First Edition Paper on November 26, 2003; DOI 10.1182/blood-2003-08-2765. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-08-2765v1 103/6/2238    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zaunders, J. J. Articles by Kelleher, A. D. Search for Related Content PubMed PubMed Citation Articles by Zaunders, J. J. Articles by Kelleher, A. D. Related Collections Immunobiology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Identification of circulating antigen-specific CD4+ T lymphocytes with a CCR5+, cytotoxic phenotype in an HIV-1 long-term nonprogressor and in CMV infection John J. Zaunders, Wayne B. Dyer, Bin Wang, Mee Ling Munier, Monica Miranda-Saksena, Rebecca Newton, John Moore, Charles R. Mackay, David A. Cooper, Nitin K. Saksena, and Anthony D. Kelleher From the Centre for Immunology, St Vincent's Hospital and University of New South Wales, Sydney, Australia; Viral Immunology Laboratory, Tissue Typing Department, Australian Red Cross Blood Service, Sydney, Australia; Retroviral Genetics Laboratory, Centre for Virus Research, Westmead Millennium Institute, Westmead Hospital and University of Sydney, Sydney, Australia; National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia; Garvan Institute, Sydney, Australia; and the Haematology Department, St Vincent's Hospital, Sydney, Australia. Antigen-specific CD4+ effector T cells primarily provide help for B-cell antibody responses and CD8+ cytotoxic T-lymphocyte (CTL) responses. We have found an expanded population of HIV-1 p24-specific, T-cell receptor Vbeta17+, CD4+ T lymphocytes, defined by in vitro proliferative and interferon- responses to a 15-mer Gag peptide, in the peripheral blood of an individual with long-term nonprogressive HIV-1 infection. Ex vivo, these cells were CCR5+ and CCR7-, consistent with an effector/memory function. Surprisingly, these cells highly expressed several proteins characteristic of cytotoxic lymphocytes, including TIA-1 (T-cell intracellular antigen 1; GMP-17/NKG7), granzymes A and B, CD161 (NKRP-1), and CD244 (C1.7/2B4). Following in vitro peptide stimulation, these cells produced interleukin 2 (IL-2) and intracellular CD40L, suggesting possible helper function, in addition to induction of perforin and cytotoxicity. A subset of cytomegalovirus (CMV)–specific CD4+ T cells in healthy adults similarly expressed these CTL markers and CCR5, ex vivo. Furthermore, this distinct subset of CD4+ T cells was significantly elevated in healthy CMV-seropositive adults, compared with CMV-seronegative individuals. These results suggest that CCR5+ CD4+ CTL may be a major effector mechanism of the immune response to viral infections in humans. Moreover, expression of CCR5 may render them particularly susceptible to cytopathic effects during progressive HIV-1 infection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Karlsson, B. Malleret, P. Brochard, B. Delache, J. Calvo, R. Le Grand, and B. Vaslin Dynamics of T-Cell Responses and Memory T Cells during Primary Simian Immunodeficiency Virus Infection in Cynomolgus Macaques J. Virol., December 15, 2007; 81(24): 13456 - 13468. [Abstract] [Full Text] [PDF] S. J. Potter, C. Lacabaratz, O. Lambotte, S. Perez-Patrigeon, B. Vingert, M. Sinet, J.-H. Colle, A. Urrutia, D. Scott-Algara, F. Boufassa, et al. 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