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

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.