biostudies-literatureMakatsa MSHHS | National Institutes of HealthHHS | NIH | NIH Office of the DirectorFrancis Crick InstituteEuropean & Developing Countries Clinical Trials Partnership (EDCTP)NIAID NIH HHSThe Francis Crick InstituteSouth African Medical Research CouncilWellcome TrustEC | H2020 | ERA-LEARN | European and Developing Countries Clinical Trials PartnershipNational Health Laboratory Service446-455https://www.ebi.ac.uk/biostudies/studies/S-EPMC9339498biostudies-literatureUnknown209(3)The development of a highly effective tuberculosis (TB) vaccine is likely dependent on our understanding of what constitutes a protective immune response to TB. Accumulating evidence suggests that CD4⁺ T cells producing IL-22, a distinct subset termed "Th22" cells, may contribute to protective immunity to TB. Thus, we characterized <i>Mycobacterium tuberculosis</i>-specific Th22 (and Th1 and Th17) cells in 72 people with latent TB infection or TB disease, with and without HIV-1 infection. We investigated the functional properties (IFN-γ, IL-22, and IL-17 production), memory differentiation (CD45RA, CD27, and CCR7), and activation profile (HLA-DR) of <i>M. tuberculosis</i>-specific CD4⁺ T cells. In HIV-uninfected individuals with latent TB infection, we detected abundant circulating IFN-γ-producing CD4⁺ T cells (median, 0.93%) and IL-22-producing CD4⁺ T cells (median, 0.46%) in response to <i>M. tuberculosis</i> The frequency of IL-17-producing CD4⁺ T cells was much lower, at a median of 0.06%. Consistent with previous studies, IL-22 was produced by a distinct subset of CD4⁺ T cells and not coexpressed with IL-17. <i>M. tuberculosis</i>-specific IL-22 responses were markedly reduced (median, 0.08%) in individuals with TB disease and HIV coinfection compared with IFN-γ responses. <i>M. tuberculosis</i>-specific Th22 cells exhibited a distinct memory and activation phenotype compared with Th1 and Th17 cells. Furthermore, <i>M. tuberculosis</i>-specific IL-22 was produced by conventional CD4⁺ T cells that required TCR engagement. In conclusion, we confirm that Th22 cells are a component of the human immune response to TB. Depletion of <i>M. tuberculosis</i>-specific Th22 cells during HIV coinfection may contribute to increased risk of TB disease.Journal of immunology (Baltimore, Md. : 1950)Characterization of <i>Mycobacterium tuberculosis</i>-Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection.PMC93394982016-2DEV04U01 AI11594092755TMA2016SF-1535203135 and 104803TMA2016SF-1535-CaTCH-22TMA2017SF-1951203135R21 AI11597710218R21AI115977104803/Z/14/ZCC2112FC0010218104803TMA2017SF-1951-TB-SpecBunjun ROmondi FMARiou CWilkinson RJMakatsa MSBurgers WAfalseCharacterization of <i>Mycobacterium tuberculosis</i>-Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection.The development of a highly effective tuberculosis (TB) vaccine is likely dependent on our understanding of what constitutes a protective immune response to TB. Accumulating evidence suggests that CD4⁺ T cells producing IL-22, a distinct subset termed "Th22" cells, may contribute to protective immunity to TB. Thus, we characterized <i>Mycobacterium tuberculosis</i>-specific Th22 (and Th1 and Th17) cells in 72 people with latent TB infection or TB disease, with and without HIV-1 infection. We investigated the functional properties (IFN-γ, IL-22, and IL-17 production), memory differentiation (CD45RA, CD27, and CCR7), and activation profile (HLA-DR) of <i>M. tuberculosis</i>-specific CD4⁺ T cells. In HIV-uninfected individuals with latent TB infection, we detected abundant circulating IFN-γ-producing CD4⁺ T cells (median, 0.93%) and IL-22-producing CD4⁺ T cells (median, 0.46%) in response to <i>M. tuberculosis</i> The frequency of IL-17-producing CD4⁺ T cells was much lower, at a median of 0.06%. Consistent with previous studies, IL-22 was produced by a distinct subset of CD4⁺ T cells and not coexpressed with IL-17. <i>M. tuberculosis</i>-specific IL-22 responses were markedly reduced (median, 0.08%) in individuals with TB disease and HIV coinfection compared with IFN-γ responses. <i>M. tuberculosis</i>-specific Th22 cells exhibited a distinct memory and activation phenotype compared with Th1 and Th17 cells. Furthermore, <i>M. tuberculosis</i>-specific IL-22 was produced by conventional CD4⁺ T cells that required TCR engagement. In conclusion, we confirm that Th22 cells are a component of the human immune response to TB. Depletion of <i>M. tuberculosis</i>-specific Th22 cells during HIV coinfection may contribute to increased risk of TB disease.2022-01-01T00:00:00Z2022 Aug2024-12-04T05:13:23.942Z2024-12-04T05:13:23.942ZS-EPMC93394983577784810.4049/jimmunol.2200140