Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 35, Issue 1, Pages 159-170Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/eji.200425744
Keywords
HIV-1; dendritic cells; CD8(+) T cell response; cellular proliferation
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Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R56AI040045, P30AI042848, R01AI040045, R37AI040045] Funding Source: NIH RePORTER
- NIAID NIH HHS [AI 40045, P30 AI042848] Funding Source: Medline
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Chronically HIV-1-infected patients fail to contain their viremia despite high frequencies of HIV-1-specific, IFN-gamma-producing CD8(+) T cells. However, these cells are known to exhibit both phenotypic and functional defects. We tested if mature dendritic cells (DC) could correct defective HIV-1 gag-specific T cell responses and if responses to other viral antigens were comparably affected. The circulating gag-specific CD8(+) T cells in fresh blood reliably produced IFN-gamma but lacked IL-2 and high perforin levels and failed to expand significantly during culture with mature DC presenting HIV-1 gag peptides. In contrast, CD8(+) T cells from long-term nonprogressors contained gag-specific IFN-gamma and IL-2 double producers, and the numbers of IFN-gamma producers expanded similar to15-fold during culture with DC. DC from chronically infected patients could expand IFN-gamma- and IL-2-producing cells specific for influenza, cytornegalovirus and Epstein Barr virus, and the expansions were comparable to those in healthy donors. When the proliferative capacity of CD8(+) T cells from progressor patients was assessed by CFSE dilution, proliferation to other viral antigens was more vigorous than to HIV-1 gag. Therefore, monocyte-derived DC from HIV patients present viral antigens effectively, but there is a selective inability to expand CD8(+) IFN-gamma-producing and IFN-gamma and IL-2 double-producing T cells when challenged with HIV-1 gag.
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