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Gut commensal microbes do not represent a dominant antigenic source for continuous CD4+T-cell activation during HIV-1 infection


Zimmermann, Kathrin; Bastidas, Sonia; Knecht, Leandra; Kuster, Herbert; Vavricka, Stephan R; Günthard, Huldrych F; Oxenius, Annette (2015). Gut commensal microbes do not represent a dominant antigenic source for continuous CD4+T-cell activation during HIV-1 infection. European Journal of Immunology, 45(11):3107-3113.

Abstract

Chronic immune activation is a hallmark of HIV-1 infection; specifically, the activation of T cells has predictive value for progression to AIDS. The majority of hyperactivated T cells are not HIV-specific and their antigenic specificities remain poorly understood. Translocation of gut luminal microbial products to systemic sites contributes to chronic immune activation during HIV-1 infection, but how it affects (TCR-dependent) immune activation remains elusive. We hypothesized that gut luminal antigens foster activation of CD4+ T cells with specificities for commensal bacterial antigens, thereby contributing to the pool of activated CD4+ T cells in the circulation of HIV-1 infected individuals. To test this hypothesis, we quantified the frequencies of gut microbe-specific CD4+ T cells by cytokine production upon restimulation with selected gut commensal microbial antigens. Contrary to our hypothesis, we did not observe increased but rather decreased frequencies of gut microbe-specific CD4+ T cells in HIV-1 infected individuals compared to healthy controls. We conclude that the increased activation status of circulating CD4+ T cells in HIV-1 infected individuals is not driven by CD4+ T cells with specificities for commensal bacterial antigens.

Abstract

Chronic immune activation is a hallmark of HIV-1 infection; specifically, the activation of T cells has predictive value for progression to AIDS. The majority of hyperactivated T cells are not HIV-specific and their antigenic specificities remain poorly understood. Translocation of gut luminal microbial products to systemic sites contributes to chronic immune activation during HIV-1 infection, but how it affects (TCR-dependent) immune activation remains elusive. We hypothesized that gut luminal antigens foster activation of CD4+ T cells with specificities for commensal bacterial antigens, thereby contributing to the pool of activated CD4+ T cells in the circulation of HIV-1 infected individuals. To test this hypothesis, we quantified the frequencies of gut microbe-specific CD4+ T cells by cytokine production upon restimulation with selected gut commensal microbial antigens. Contrary to our hypothesis, we did not observe increased but rather decreased frequencies of gut microbe-specific CD4+ T cells in HIV-1 infected individuals compared to healthy controls. We conclude that the increased activation status of circulating CD4+ T cells in HIV-1 infected individuals is not driven by CD4+ T cells with specificities for commensal bacterial antigens.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2015
Deposited On:01 Feb 2016 08:58
Last Modified:08 Dec 2017 18:33
Publisher:Wiley-VCH Verlag Berlin
ISSN:0014-2980
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/eji.201545940

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