Gut commensal microbes do not represent a dominant antigenic source for continuous CD4+ T-cell activation during HIV-1 infection.
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.
Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
Kathrin
K
Zimmermann
Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
Sonia
S
Bastidas
Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
Leandra
L
Knecht
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Herbert
H
Kuster
Division of Gastroenterology and Hepatology, Triemli Hospital, Zurich, Switzerland.
Stephan R
SR
Vavricka
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.|Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Huldrych F
HF
Günthard
Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
Annette
A
Oxenius
D000942:Antigens, Bacterial / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D002986:Clinical Trials as Topic; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*
D000942:Antigens, Bacterial
Gut microbe-specific CD4+ T-cell responses; IBD and HIV-1 associated enteropathy; Microbial translocation; Systemic immune activation