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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1660-1667. Prepublished online as a Blood First Edition Paper on May 19, 2005; DOI 10.1182/blood-2005-01-0206. This Article Full Text (PDF) All Versions of this Article: 2005-01-0206v1 106/5/1660    most recent Alert me when this article is cited Alert me if a correction is posted 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 18, 2005 Accepted April 22, 2005 Early proliferation of CCR5+ CD38+++ antigen-specific CD4+ Th1 effector cells during primary HIV-1 infection John J Zaunders*, Mee Ling Munier, Daniel E Kaufmann, Susanna Ip, Pat Grey, Don Smith, Tim Ramacciotti, Dick Quan, Robert Finlayson, John Kaldor, Eric S Rosenberg, Bruce D Walker, David A Cooper, and Anthony D Kelleher Centre for Immunology, St. Vincent's Hospital, Sydney, NSW, Australia Centre for Immunology, St. Vincent's Hospital, Sydney, NSW, Australia; National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, NSW, Australia Partners AIDS Research Center, Massachusetts General Hospital, Boston, MA, USA National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, NSW, Australia Holdsworth House General Practice, Sydney, NSW, Australia Taylor Square Private Clinic, Sydney, NSW, Australia * Corresponding author; email: j.zaunders{at}cfi.unsw.edu.au. We investigated whether HIV-1 antigen-specific CD4+ T cells expressed the viral co-receptor, CCR5, during primary HIV-1 infection (PHI). In the peripheral blood of subjects with very early PHI (< 22 days post-onset of symptoms), there was a 10 to 20-fold increase in the proportion of highly activated (CD38+++) and proliferating (Ki-67+) CD4+ T cells which expressed CCR5+, and were mostly TIA-1+perforin+granzymeB+. In the same patient samples, CD4+ T cells producing IFN- in response to HIV Gag peptides were readily detected (median 0.58%) by intracellular cytokine assay - these cells were again predominantly CD38+++, Ki-67+ and TIA-1+, as well as Bcl-2low. On average, 20% of the Gag-specific CD4+ T cells also expressed IL-2 and were CD127(IL-7R)+. Taken together, these results suggest that Gag-specific Th1 effector cells express CCR5+ during the primary response and may include precursors of long-term self-renewing memory cells. However, in PHI subjects with later presentation, antigen-specific CD4+ T cells could not be readily detected (median 0.08%), coinciding with a 5-fold lower level of the CCR5+CD38+++ CD4+ T cells. These results suggest that the anti-viral response to HIV-1 infection includes highly activated CCR5+CD4+ cytotoxic effector cells, which are susceptible to both apoptosis and cytopathic infection with HIV-1, and rapidly decline. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Malavasi, S. Deaglio, A. Funaro, E. Ferrero, A. L. Horenstein, E. Ortolan, T. Vaisitti, and S. Aydin Evolution and Function of the ADP Ribosyl Cyclase/CD38 Gene Family in Physiology and Pathology Physiol Rev, July 1, 2008; 88(3): 841 - 886. [Abstract] [Full Text] [PDF] C. F. Thobakgale, D. Ramduth, S. Reddy, N. Mkhwanazi, C. de Pierres, E. Moodley, W. Mphatswe, N. Blanckenberg, A. Cengimbo, A. Prendergast, et al. Human Immunodeficiency Virus-Specific CD8+ T-Cell Activity Is Detectable from Birth in the Majority of In Utero-Infected Infants J. Virol., December 1, 2007; 81(23): 12775 - 12784. [Abstract] [Full Text] [PDF] E. Rutjens, S. Mazza, R. Biassoni, G. Koopman, L. Radic, M. Fogli, P. Costa, M. C. Mingari, L. Moretta, J. Heeney, et al. Differential NKp30 Inducibility in Chimpanzee NK Cells and Conserved NK Cell Phenotype and Function in Long-Term HIV-1-Infected Animals J. Immunol., February 1, 2007; 178(3): 1702 - 1712. [Abstract] [Full Text] [PDF] J. J. Zaunders, W. B. Dyer, M. L. Munier, S. Ip, J. Liu, E. Amyes, W. Rawlinson, R. De Rose, S. J. Kent, J. S. Sullivan, et al. CD127+CCR5+CD38+++ CD4+ Th1 Effector Cells Are an Early Component of the Primary Immune Response to Vaccinia Virus and Precede Development of Interleukin-2+ Memory CD4+ T Cells. J. Virol., October 1, 2006; 80(20): 10151 - 10161. [Abstract] [Full Text] [PDF] J. J. Zaunders, S. Ip, M. L. Munier, D. E. Kaufmann, K. Suzuki, C. Brereton, S. C. Sasson, N. Seddiki, K. Koelsch, A. Landay, et al. Infection of CD127+ (Interleukin-7 Receptor+) CD4+ Cells and Overexpression of CTLA-4 Are Linked to Loss of Antigen-Specific CD4 T Cells during Primary Human Immunodeficiency Virus Type 1 Infection. J. Virol., October 1, 2006; 80(20): 10162 - 10172. [Abstract] [Full Text] [PDF]

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