A paper recently published online by the journal Blood offers new data on HIV-specific CD8 T cell responses in the rectal mucosa of elite controllers (individuals who control HIV replication to undetectable levels in the absence of treatment). The senior investigator, Barbara Shacklett, generously took time out to discuss the study findings with TAG and the interview is posted on the our website.
Blood First Edition Paper, prepublished online December 23, 2008; DOI 10.1182/blood-2008-10-182709.
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
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.
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