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Adenovirus Serotype 5 Vectors Trigger IL-27-Dependent Inhibitory CD4+ T Cell Responses

Rafael Assumpção Larocca, Nicholas M Provine, Mark Justin Iampietro, Erica N Borducchi, Pablo A Penaloza-MacMaster, Alexander Badamchi-Zadeh, Christine A Bricault, Eryn Blass, Lily R Parenteau, Stephen Blackmore, Kathryn E Stephenson and Dan H Barouch
J Immunol May 1, 2016, 196 (1 Supplement) 196.10;
Rafael Assumpção Larocca
Beth Israel Deaconess Med. Ctr.
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Nicholas M Provine
Beth Israel Deaconess Med. Ctr.
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Mark Justin Iampietro
Beth Israel Deaconess Med. Ctr.
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Erica N Borducchi
Beth Israel Deaconess Med. Ctr.
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Pablo A Penaloza-MacMaster
Beth Israel Deaconess Med. Ctr.
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Alexander Badamchi-Zadeh
Beth Israel Deaconess Med. Ctr.
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Christine A Bricault
Beth Israel Deaconess Med. Ctr.
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Eryn Blass
Beth Israel Deaconess Med. Ctr.
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Lily R Parenteau
Beth Israel Deaconess Med. Ctr.
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Stephen Blackmore
Beth Israel Deaconess Med. Ctr.
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Kathryn E Stephenson
Beth Israel Deaconess Med. Ctr.
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Dan H Barouch
Beth Israel Deaconess Med. Ctr. Ragon Inst. of MGH, MIT and Harvard
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Abstract

Viral vectors are attractive vaccine platforms that elicit robust innate and adaptive immune responses, but they vary greatly in their ability to induce protective immunity. Adenovirus serotype 5 (Ad5) vectors elicit robust CD8+ T cell responses but are typically characterized by an exhausted phenotype. The mechanisms by which Ad5 vectors induce dysfunctional CD8+ T cells have not been fully elucidated. Here we demonstrate that Ad5 vectors, but not Ad26 vectors, elicit exhausted antigen-specific IL-10+PD1+ CD4+ T cells with a dysfunctional transcriptional profile, and these cells effectively suppress CD8+ T cell responses in vivo. The blockade of IL-10 increased the frequency of antigen-specific CD8+ T cells with enhanced cytokine polyfunctionality and protective capacity against a Listeria monocytogenes challenge. Induction of inhibitory CD4+ T cells by Ad5 vectors is associated with increased IL-27 expression, and IL-27 blockade improves CD4+ T cell cytokine polyfunctionality. Together our data highlight a novel role for IL-27 induced inhibitory CD4+ T cells in regulating responses to viral vector vaccines.

  • Copyright © 2016 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 196, Issue 1 Supplement
1 May 2016
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Adenovirus Serotype 5 Vectors Trigger IL-27-Dependent Inhibitory CD4+ T Cell Responses
Rafael Assumpção Larocca, Nicholas M Provine, Mark Justin Iampietro, Erica N Borducchi, Pablo A Penaloza-MacMaster, Alexander Badamchi-Zadeh, Christine A Bricault, Eryn Blass, Lily R Parenteau, Stephen Blackmore, Kathryn E Stephenson, Dan H Barouch
The Journal of Immunology May 1, 2016, 196 (1 Supplement) 196.10;

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Adenovirus Serotype 5 Vectors Trigger IL-27-Dependent Inhibitory CD4+ T Cell Responses
Rafael Assumpção Larocca, Nicholas M Provine, Mark Justin Iampietro, Erica N Borducchi, Pablo A Penaloza-MacMaster, Alexander Badamchi-Zadeh, Christine A Bricault, Eryn Blass, Lily R Parenteau, Stephen Blackmore, Kathryn E Stephenson, Dan H Barouch
The Journal of Immunology May 1, 2016, 196 (1 Supplement) 196.10;
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Print ISSN 0022-1767        Online ISSN 1550-6606