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Clinical and Vaccine Immunology, October 2009, p. 1504-1516, Vol. 16, No. 10
1071-412X/09/$08.00+0     doi:10.1128/CVI.00104-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Multiple T-Cell Responses to Human Immunodeficiency Virus Type 1 Are Enhanced by Dendritic Cells {triangledown} ,{dagger}

Xiao-Li Huang, Zheng Fan, LuAnn Borowski, and Charles R. Rinaldo*

Graduate School of Public Health and School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

Received 7 March 2009/ Returned for modification 6 May 2009/ Accepted 10 August 2009

Human immunodeficiency virus type 1 (HIV-1)-specific T-cell reactivity has been related to protection from disease progression. Optimal T-cell reactivity to HIV-1 presumably requires antigen processing and presentation by professional antigen-presenting cells, particularly dendritic cells (DC). Here we examined whether multiple HIV-1-specific T-cell functions are enhanced by stimulation with HIV-1 peptide-loaded DC derived from HIV-1-infected subjects on antiretroviral therapy. We first found that mature DC increased the number of gamma interferon (IFN-{gamma})-producing T cells detected by enzyme-linked immunospot assay to overlapping 15-mer peptides of HIV-1 Gag and Nef, compared to stimulation with peptide-loaded, immature DC or to peptides without DC. IFN-{gamma} production was lower in response to large pools of the Gag and Nef peptides, regardless of presentation by DC. We further observed that HIV-1 peptide-loaded, mature DC stimulated greater CD8+ and CD4+ T-cell proliferation than did the peptides without DC and that T-cell proliferation was lower in response to larger pools of the peptides. The lower T-cell IFN-{gamma} and proliferation responses to the larger peptide pools were related to lower T-cell viability. Finally, the number of polyfunctional CD8+ and CD4+ T cells stimulated by HIV-1 peptide-loaded, mature DC, defined as positive by intracellular staining for more than one immune mediator (IFN-{gamma}, interleukin 2, tumor necrosis factor alpha, macrophage inhibitory protein 1β, or CD107a), was greater than that stimulated by the peptides alone. These results indicate that DC can enhance multiple types of HIV-1-specific T-cell functions.

* Corresponding author. Mailing address: A419 Crabtree Hall, University of Pittsburgh Graduate School of Public Health, 130 DeSoto Street, Pittsburgh, PA 15261. Phone: (412) 624-3928. Fax: (412) 624-4953. E-mail: rinaldo{at}pitt.edu

{triangledown} Published ahead of print on 19 August 2009.

{dagger} Supplemental material for this article may be found at http://cvi.asm.org/.

Clinical and Vaccine Immunology, October 2009, p. 1504-1516, Vol. 16, No. 10
1071-412X/09/$08.00+0     doi:10.1128/CVI.00104-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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