Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulate gag-Specific Immune Responses

A variety of immune-based therapies has been developed in order to boost or induce protective CD8+ T cell responses in order to control HIV replication. Since dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique capability to stimulate naïve T cells into effector T...

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Main Authors: Ellen Van Gulck, Nathalie Cools, Derek Atkinson, Lotte Bracke, Katleen Vereecken, Marc Vekemans, Viggo F. I. Van Tendeloo, Zwi N. Berneman, Guido Vanham
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2012/184979
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author Ellen Van Gulck
Nathalie Cools
Derek Atkinson
Lotte Bracke
Katleen Vereecken
Marc Vekemans
Viggo F. I. Van Tendeloo
Zwi N. Berneman
Guido Vanham
author_facet Ellen Van Gulck
Nathalie Cools
Derek Atkinson
Lotte Bracke
Katleen Vereecken
Marc Vekemans
Viggo F. I. Van Tendeloo
Zwi N. Berneman
Guido Vanham
author_sort Ellen Van Gulck
collection DOAJ
description A variety of immune-based therapies has been developed in order to boost or induce protective CD8+ T cell responses in order to control HIV replication. Since dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique capability to stimulate naïve T cells into effector T cells, their use for the induction of HIV-specific immune responses has been studied intensively. In the present study we investigated whether modulation of the activation state of DCs electroporated with consensus codon-optimized HxB2 gag mRNA enhances their capacity to induce HIV gag-specific T cell responses. To this end, mature DCs were (i) co-electroporated with mRNA encoding interleukin (IL)-12p70 mRNA, or (ii) activated with a cytokine cocktail consisting of R848 and interferon (IFN)-γ. Our results confirm the ability of HxB2 gag-expressing DCs to expand functional HIV-specific CD8+ T cells. However, although most of the patients had detectable gag-specific CD8+ T cell responses, no significant differences in the level of expansion of functional CD8+ T cells could be demonstrated when comparing conventional or immune-modulated DCs expressing IL-12p70. This result which goes against expectation may lead to a re-evaluation of the need for IL-12 expression by DCs in order to improve T-cell responses in HIV-1-infected individuals.
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spelling doaj-art-4f4ef63f4f194d7eb9a4193900256c442025-02-03T06:11:07ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/184979184979Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulate gag-Specific Immune ResponsesEllen Van Gulck0Nathalie Cools1Derek Atkinson2Lotte Bracke3Katleen Vereecken4Marc Vekemans5Viggo F. I. Van Tendeloo6Zwi N. Berneman7Guido Vanham8Virology Unit, Department of Microbiology, Institute of Tropical Medicine (ITMA), 2000 Antwerp, BelgiumLaboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, BelgiumVirology Unit, Department of Microbiology, Institute of Tropical Medicine (ITMA), 2000 Antwerp, BelgiumVirology Unit, Department of Microbiology, Institute of Tropical Medicine (ITMA), 2000 Antwerp, BelgiumVirology Unit, Department of Microbiology, Institute of Tropical Medicine (ITMA), 2000 Antwerp, BelgiumUnit of HIV/STD, Department of Clinical Sciences, ITMA, 2000 Antwerp, BelgiumLaboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, BelgiumLaboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, BelgiumVirology Unit, Department of Microbiology, Institute of Tropical Medicine (ITMA), 2000 Antwerp, BelgiumA variety of immune-based therapies has been developed in order to boost or induce protective CD8+ T cell responses in order to control HIV replication. Since dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique capability to stimulate naïve T cells into effector T cells, their use for the induction of HIV-specific immune responses has been studied intensively. In the present study we investigated whether modulation of the activation state of DCs electroporated with consensus codon-optimized HxB2 gag mRNA enhances their capacity to induce HIV gag-specific T cell responses. To this end, mature DCs were (i) co-electroporated with mRNA encoding interleukin (IL)-12p70 mRNA, or (ii) activated with a cytokine cocktail consisting of R848 and interferon (IFN)-γ. Our results confirm the ability of HxB2 gag-expressing DCs to expand functional HIV-specific CD8+ T cells. However, although most of the patients had detectable gag-specific CD8+ T cell responses, no significant differences in the level of expansion of functional CD8+ T cells could be demonstrated when comparing conventional or immune-modulated DCs expressing IL-12p70. This result which goes against expectation may lead to a re-evaluation of the need for IL-12 expression by DCs in order to improve T-cell responses in HIV-1-infected individuals.http://dx.doi.org/10.1155/2012/184979
spellingShingle Ellen Van Gulck
Nathalie Cools
Derek Atkinson
Lotte Bracke
Katleen Vereecken
Marc Vekemans
Viggo F. I. Van Tendeloo
Zwi N. Berneman
Guido Vanham
Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulate gag-Specific Immune Responses
Clinical and Developmental Immunology
title Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulate gag-Specific Immune Responses
title_full Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulate gag-Specific Immune Responses
title_fullStr Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulate gag-Specific Immune Responses
title_full_unstemmed Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulate gag-Specific Immune Responses
title_short Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulate gag-Specific Immune Responses
title_sort interleukin 12p70 expression by dendritic cells of hiv 1 infected patients fails to stimulate gag specific immune responses
url http://dx.doi.org/10.1155/2012/184979
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