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Regulatory T cell suppression of gag-specific CD8<sup>+</sup> T cell polyfunctional response after therapeutic vaccination of HIV-1-infected patients on ART

Macatangay, BJC and Szajnik, ME and Whiteside, TL and Riddler, SA and Rinaldo, CR (2010) Regulatory T cell suppression of gag-specific CD8<sup>+</sup> T cell polyfunctional response after therapeutic vaccination of HIV-1-infected patients on ART. PLoS ONE, 5 (3).

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We tested the hypothesis that therapeutic vaccination against HIV-1 can increase the frequency and suppressive function of regulatory, CD4+ T cells (Treg), thereby masking enhancement of HIV-1-specific CD8+ T cell response. HIV-1-infected subjects on antiretroviral therapy (N = 17) enrolled in a phase I therapeutic vaccine trial received 2 doses of autologous dendritic cells (DC) loaded with HIV-1 peptides. The frequency of CD4+CD25hiFOXP3+ Treg in blood was determined prior to and after vaccination in subjects and normal controls. Polyfunctional CD8+ T cell responses were determined pre- and post-vaccine (N = 7) for 5 immune mediators after in vitro stimulation with Gag peptide, staphylococcal enterotoxin B (SEB), or medium alone. Total vaccine response (post-vaccine-pre-vaccine) was compared in the Treg(+) and Treg-depleted (Treg-) sets. After vaccination, 12/17 subjects showed a trend of increased Treg frequency (P = 0.06) from 0.74% to 1.2%. The increased frequency did not correlate with CD8+ T cell vaccine response by enzyme linked immunosorbent assay for interferon c production. Although there was no significant change in CD8+ T cell polyfunctional response after vaccination, Treg depletion increased the polyfunctionality of the total vaccine response (P = 0.029), with a >2-fold increase in the percentage of CD8+ T cells producing multiple immune mediators. In contrast, depletion of Treg did not enhance polyfunctional T cell response to SEB, implying specificity of suppression to HIV-1 Gag. Therapeutic immunization with a DC-based vaccine against HIV-1 caused a modest increase in Treg frequency and a significant increase in HIV-1-specific, Treg suppressive function. The Treg suppressive effect masked an increase in the vaccine-induced anti-HIV-1-specific polyfunctional response. The role of Treg should be considered in immunotherapeutic trials of HIV-1 infection. © 2010 Macatangay et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Macatangay, BJC
Szajnik, ME
Whiteside, TL
Riddler, SAriddler@pitt.eduRIDDLER
Rinaldo, CRRINALDO@pitt.eduRINALDO
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 1 December 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 3
DOI or Unique Handle: 10.1371/journal.pone.0009852
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
MeSH Headings: AIDS Vaccines--therapeutic use; Anti-Retroviral Agents; CD8-Positive T-Lymphocytes--cytology; Dendritic Cells--cytology; Enzyme-Linked Immunosorbent Assay--methods; Female; HIV Infections--immunology; HIV Infections--metabolism; HIV-1--genetics; Humans; Immunophenotyping; Interferon-gamma--metabolism; Leukocytes, Mononuclear--cytology; Male; T-Lymphocytes, Regulatory--immunology; gag Gene Products, Human Immunodeficiency Virus--metabolism
Other ID: NLM PMC2844424
PubMed Central ID: PMC2844424
PubMed ID: 20352042
Date Deposited: 03 Aug 2012 18:56
Last Modified: 22 Jun 2021 16:55


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