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Blood, 23 April 2009, Vol. 113, No. 17, pp. 3978-3989. Prepublished online as a Blood First Edition Paper on December 23, 2008; DOI 10.1182/blood-2008-10-182709. This Article Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2008-10-182709v1 113/17/3978    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 Ferre, A. L Articles by Shacklett, B. L Search for Related Content PubMed PubMed Citation Articles by Ferre, A. L Articles by Shacklett, B. L Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 6, 2008 Accepted December 16, 2008 Mucosal immune responses to HIV-1 in elite controllers: A potential correlate of immune control April L Ferre, Peter W. Hunt, J. William Critchfield, Delandy H Young, Megan M Morris, Juan C. Garcia, Richard B Pollard, Hal F Yee Jr., Jeffrey N Martin, Steven G Deeks, and Barbara L Shacklett* Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA, United States Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, United States Division of Gastroenterology, Department of Medicine, School of Medicine, University of California, Davis, CA, United States Division of Infectious Diseases, Department of Medicine, School of Medicine, University of California, Davis, CA, United States Division of Gastroenterology, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, United States Department of Epidemiology and Biostatistics, San Francisco General Hospital, University of California, San Francisco, CA, United States * Corresponding author; email: blshacklett{at}ucdavis.edu. There exists a unique group of individuals who are able to durably control HIV in the absence of therapy. The mechanisms of control in these individuals remain poorly defined. In this study we examined CD8+ T-cell responses in blood and rectal mucosa from 17 "elite controllers" (viral load < 75 copies/ml), 11 "viremic controllers" (75-2,000 copies/mL), 14 non-controllers (>10,000 copies/mL), and 10 antiretroviral-treated individuals (<75 copies/mL). Production of IFN-, IL-2, TNF-, MIP-1, and CD107a by CD8+ T-cells in response to HIV-1 Gag stimulation was measured using flow cytometry. Our hypothesis was that 'polyfunctional' T-cells producing multiple antiviral factors would be most abundant in mucosal tissues of HIV controllers. Mucosal CD8+ T-cell responses were significantly stronger and more complex in controllers than in antiretroviral-suppressed individuals (P=0.0004). The frequency of 4-function responses in rectal mucosa was higher in controllers than in non-controllers and patients on therapy (P<0.0001). Mucosal responses in controllers were frequently stronger and more complex than blood responses. These findings demonstrate that many controllers mount strong, complex HIV-specific T-cell responses in rectal mucosa. These responses may play an important role in mucosal immune surveillance, as suggested by their relative enrichment among individuals who control HIV in the absence of therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X.-L. Huang, Z. Fan, L. Borowski, and C. R. Rinaldo Multiple T-Cell Responses to Human Immunodeficiency Virus Type 1 Are Enhanced by Dendritic Cells Clin. Vaccine Immunol., October 1, 2009; 16(10): 1504 - 1516. [Abstract] [Full Text] [PDF]

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