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Volume 6 Supplement 3

AIDS Vaccine 2009

OA031-03. Increased regulatory T cell frequency and HIV-1 specific suppression after therapeutic vaccination of HIV-infected patients on antiretroviral therapy

Background

We tested the hypothesis that therapeutic vaccination against HIV-1 can lead to an increase in the frequency and suppressive function of regulatory, CD4+ T cells (Treg).

Methods

HIV-1(+) subjects on ART (n = 17) were enrolled in a phase I therapeutic vaccine trial where they received 2 doses of autologous dendritic cells loaded with HIV-1 peptides. Peripheral blood mononuclear cells (PBMC) obtained from the subjects pre- and post-vaccine, and from normal controls (NC) were stained with antibodies specific for Treg (CD4+CD25hiFOXP3+), CD45RO, GITR, and CTLA4 and assayed by flow cytometry. PBMC pre and post-vaccine from 7 subjects were also evaluated for polyfunctionality using a flow cytometry-based, CD8+ T cell intracellular cytokine staining assay for 5 immune mediators after stimulation with Gag peptide, staphylococcal enterotoxin B (SEB) and medium alone. Treg were depleted in one set, and total vaccine response (post-vaccine - pre-vaccine) was compared in the Treg(+) and Treg-depleted (Treg-) sets.

Results

After vaccination, 12/17 subjects had increased Treg frequency from 0.74% to 1.2% (p = 0.06); the median increase was 30%. Of the 11 patients whose CD8+ T cells did not respond to the vaccine by an increase in production of interferon γ (ELISPOT assay), 7 (64%) had increased frequencies of Treg. Although there was no significant change in CD8+ T cell polyfunctionality after vaccination, depletion of Treg resulted in increased polyfunctionality post-vaccine (p = 0.029), with the percentage of CD8+ T cells producing more than 1 immune mediator increasing to more than twice the pre-vaccine levels. There was no difference in polyfunctionality in the Treg(+) and Treg(-) sets when stimulated with SEB, implying specificity of suppression to HIV-1 antigens.

Conclusion

Therapeutic immunization against HIV-1 causes a modest increase in Treg frequency and a significant increase in HIV-1-specific, Treg suppressive function. The role of Treg should be considered in immunotherapeutic trials of HIV-1 infection.

Author information

Correspondence to BC Macatangay.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Peripheral Blood Mononuclear Cell
  • Suppressive Function
  • ELISPOT Assay
  • Immune Mediator
  • Staphylococcal Enterotoxin