relation: http://d-scholarship-dev.library.pitt.edu/13342/
title: Regulatory T cell suppression of gag-specific CD8<sup>+</sup> T cell polyfunctional response after therapeutic vaccination of HIV-1-infected patients on ART
creator: Macatangay, BJC
creator: Szajnik, ME
creator: Whiteside, TL
creator: Riddler, SA
creator: Rinaldo, CR
description: 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.
date: 2010-12-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/13342/1/Regulatory_T_Cell.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/13342/8/licence.txt
identifier:   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).       
relation: 10.1371/journal.pone.0009852