Dendritic cells reveal a broad range of MHC class I epitopes for HIV-1 in persons with suppressed viral load on antiretroviral therapy

Huang, XL and Fan, Z and Borowski, LA and Mailliard, RB and Rolland, M and Mullins, JI and Day, RD and Rinaldo, CR (2010) Dendritic cells reveal a broad range of MHC class I epitopes for HIV-1 in persons with suppressed viral load on antiretroviral therapy. PLoS ONE, 5 (9).

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Abstract

Background: HIV-1 remains sequestered during antiretroviral therapy (ART) and can resume high-level replication upon cessation of ART or development of drug resistance. Reactivity of memory CD8+ T lymphocytes to HIV-1 could potentially inhibit this residual viral replication, but is largely muted by ART in relation to suppression of viral antigen burden. Dendritic cells (DC) are important for MHC class I processing and presentation of peptide epitopes to memory CD8+ T cells, and could potentially be targeted to activate memory CD8+ T cells to a broad array of HIV-1 epitopes during ART. Principal Findings: We show for the first time that HIV-1 peptide-loaded, CD40L-matured DC from HIV-1 infected persons on ART induce IFN gamma production by CD8+ T cells specific for a much broader range and magnitude of Gag and Nef epitopes than do peptides without DC. The DC also reveal novel, MHC class I restricted, Gag and Nef epitopes that are able to induce polyfunctional T cells producing various combinations of IFN gamma, interleukin 2, tumor necrosis factor alpha, macrophage inhibitory protein 1 beta and the cytotoxic de-granulation molecule CD107a. Significance: There is an underlying, broad antigenic spectrum of anti-HIV-1, memory CD8+ T cell reactivity in persons on ART that is revealed by DC. This supports the use of DC-based immunotherapy for HIV-1 infection. © 2010 Huang et al.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Huang, XL Fan, Z Borowski, LA Mailliard, RB rbm19@pitt.edu RBM19 0000-0001-5501-503X Rolland, M Mullins, JI Day, RD Rinaldo, CR RINALDO@pitt.edu RINALDO
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Unutmaz, Derya UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	1 November 2010
Date Type:	Publication
Journal or Publication Title:	PLoS ONE
Volume:	5
Number:	9
DOI or Unique Handle:	10.1371/journal.pone.0012936
Schools and Programs:	School of Public Health > Biostatistics School of Public Health > Infectious Diseases and Microbiology
Refereed:	Yes
MeSH Headings:	Anti-HIV Agents--therapeutic use; CD8-Positive T-Lymphocytes--drug effects; CD8-Positive T-Lymphocytes--immunology; Cohort Studies; Cytokines--genetics; Cytokines--immunology; Dendritic Cells--drug effects; Dendritic Cells--immunology; Dendritic Cells--virology; Epitopes--genetics; Epitopes--immunology; Genes, MHC Class I; HIV Infections--drug therapy; HIV Infections--genetics; HIV Infections--immunology; HIV Infections--virology; HIV-1--drug effects; HIV-1--immunology; HIV-1--physiology; Homosexuality, Male; Humans; Lymphocyte Activation--drug effects; Male; Viral Load
Other ID:	NLM PMC2944894
PubMed Central ID:	PMC2944894
PubMed ID:	20886040
Date Deposited:	21 Aug 2012 14:18
Last Modified:	22 Jun 2021 12:55
URI:	http://d-scholarship.pitt.edu/id/eprint/13553

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