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Journal articles
Mycobacterium tuberculosis Recall Antigens Suppress HIV-1 Replication in Anergic Donor Cells via CD8+ T Cell Expansion and Increased IL-10 Levels
Abstract : Mycobacterium tuberculosis (MTb) is the leading cause of death in the setting of AIDS. MTb enhances the pathogenicity and accelerates the course of HIV disease and, furthermore, infection with HIV-1 increases the risk of reactivation or reinfection with MTb. In this study, we show that host-specific recall responses to one pathogen, MTb, has a direct effect upon the regulation of a second pathogen, HIV-1. Using cells from immunocompetent former tuberculosis (TB) patients who displayed either a persistently positive (responsive) or negative (anergic), delayed-type hypersensitivity (DTH) reaction to intradermal injection of purified protein derivative (PPD), we investigated the effect of recall Ags to MTb upon the replication of HIV-1 primary isolates in vitro. We show that HIV-1 replication of a T cell-tropic isolate was significantly impaired in MTb-stimulated PBMC from PPD-anergic donors. Furthermore, these donors displayed a significant increase in CD8 T cells and IL-10 levels and lower levels of IL-2 and TNF-relative to PPD-responsive donors in response to PPD stimulation. Strikingly, CD8 T cell depletion and blocking of IL-10 significantly increased HIV-1 replication in these PPD-anergic donors, indicating that an immunosuppressive response to MTb recall Ags inhibits HIV-1 replication in PPD-anergic individuals. Therefore, immunotherapeutic approaches aimed at recapitulating Ag-specific MTb anergy in vivo could result in novel and effective approaches to inhibit HIV-1 disease progression in MTb/HIV-1 coinfection.
Cited literature [39 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-01836686
Contributor : Jean-Marc Reynes <>
Submitted on : Thursday, July 12, 2018 - 2:41:53 PM
Last modification on : Monday, October 8, 2018 - 5:44:04 PM
Long-term archiving on: : Monday, October 15, 2018 - 4:55:26 PM
Contributor : Jean-Marc Reynes <>
Submitted on : Thursday, July 12, 2018 - 2:41:53 PM
Last modification on : Monday, October 8, 2018 - 5:44:04 PM
Long-term archiving on: : Monday, October 15, 2018 - 4:55:26 PM