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• W3189221622 endingPage "1249" @default.
• W3189221622 startingPage "1239" @default.
• W3189221622 abstract "HIV-1 infection substantially increases the risk of developing tuberculosis (TB). Mechanisms such as defects in the Th1 response to Mycobacterium tuberculosis in HIV-infected persons have been widely reported. However, Th1-independent mechanisms also contribute to protection against TB. To identify a broader spectrum of defects in TB immunity during HIV infection, we examined IL-17A and IL-22 production in response to mycobacterial Ags in peripheral blood of persons with latent TB infection and HIV coinfection. Upon stimulating with mycobacterial Ags, we observed a distinct CD4+ Th lineage producing IL-22 in the absence of IL-17A and IFN-γ. Mycobacteria-specific Th22 cells were present at high frequencies in blood and contributed up to 50% to the CD4+ T cell response to mycobacteria, comparable in magnitude to the IFN-γ Th1 response (median 0.91% and 0.55%, respectively). Phenotypic characterization of Th22 cells revealed that their memory differentiation was similar to M. tuberculosis-specific Th1 cells (i.e., predominantly early differentiated CD45RO+CD27+ phenotype). Moreover, CCR6 and CXCR3 expression profiles of Th22 cells were similar to Th17 cells, whereas their CCR4 and CCR10 expression patterns displayed an intermediate phenotype between Th1 and Th17 cells. Strikingly, mycobacterial IL-22 responses were 3-fold lower in HIV-infected persons compared with uninfected persons, and the magnitude of responses correlated inversely with HIV viral load. These data provide important insights into mycobacteria-specific Th subsets in humans and suggest a potential role for IL-22 in protection against TB during HIV infection. Further studies are needed to fully elucidate the role of IL-22 in protective TB immunity." @default.
• W3189221622 created "2021-08-16" @default.
• W3189221622 creator A5001133659 @default.
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• W3189221622 creator A5056441437 @default.
• W3189221622 date "2021-09-01" @default.
• W3189221622 modified "2023-09-27" @default.
• W3189221622 title "Th22 Cells Are a Major Contributor to the Mycobacterial CD4+ T Cell Response and Are Depleted During HIV Infection" @default.
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