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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:
CreatorsEmailPitt UsernameORCID
Huang, XL
Fan, Z
Borowski, LA
Mailliard, RBrbm19@pitt.eduRBM190000-0001-5501-503X
Rolland, M
Mullins, JI
Day, RD
Rinaldo, CRRINALDO@pitt.eduRINALDO
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorUnutmaz, DeryaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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: Graduate School of Public Health > Biostatistics
Graduate 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: 30 Mar 2021 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/13553

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