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Characterization of Mycobacterium tuberculosis-Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection.

ABSTRACT: 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 Mycobacterium tuberculosis-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 M. tuberculosis-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 M. tuberculosis 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. M. tuberculosis-specific IL-22 responses were markedly reduced (median, 0.08%) in individuals with TB disease and HIV coinfection compared with IFN-γ responses. M. tuberculosis-specific Th22 cells exhibited a distinct memory and activation phenotype compared with Th1 and Th17 cells. Furthermore, M. tuberculosis-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 M. tuberculosis-specific Th22 cells during HIV coinfection may contribute to increased risk of TB disease.

SUBMITTER: Makatsa MS

PROVIDER: S-EPMC9339498 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Characterization of Mycobacterium tuberculosis-Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection.

Makatsa Mohau S MS Omondi F Millicent A FMA Bunjun Rubina R Wilkinson Robert J RJ Riou Catherine C Burgers Wendy A WA

Journal of immunology (Baltimore, Md. : 1950) 20220701 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 Mycobacterium tuberculosis-specific Th22 (and Th1 and Th17) cells in 72 people with latent TB infection or TB disease, with and without HIV-1 infect ...[more]

PMID: 35777848

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Project description:Nearly a quarter of the global population is infected with Mycobacterium tuberculosis (Mtb), with 10 million people developing active tuberculosis (TB) annually. Co-infection with human immunodeficiency virus (HIV) has long been recognized as a significant risk factor for progression to TB disease, yet the mechanisms whereby HIV impairs T cell-mediated control of Mtb infection remain poorly defined. We hypothesized that HIV infection may promote upregulation of inhibitory receptors on Mtb-specific CD4 T cells, a mechanism that has been associated with antigen-specific T cell dysfunction in chronic infections. Using cohorts of HIV-infected and HIV-uninfected individuals with latent Mtb infection (LTBI) and with active TB disease, we stimulated peripheral blood mononuclear cells (PBMC) for 6 hours with Mtb peptide pools and evaluated co-expression profiles of the inhibitory receptors BTLA, CTLA-4, and PD-1 on IFN-γ+/TNF-α+ Mtb-specific CD4 T cells. Mtb-specific CD4 T cells in all participant groups expressed predominately either one or no inhibitory receptors, unlike cytomegalovirus- and HIV-specific CD4 T cells circulating in the same individuals, which were predominately CTLA-4+PD-1+. There were no significant differences in inhibitory receptor expression profiles of Mtb-specific CD4 T cells between HIV-uninfected and HIV-infected individuals with LTBI. Surprisingly, BTLA expression, both alone and in combination with CTLA-4 and PD-1, was markedly downregulated on Mtb-specific CD4 T cells in HIV-infected individuals with active TB. Together, these data provide novel evidence that the majority of Mtb-specific CD4 T cells do not co-express multiple inhibitory receptors, regardless of HIV infection status; moreover, they highlight a previously unrecognized role of BTLA expression on Mtb-specific CD4 T cells that could be further explored as a potential biomarker of Mtb infection status, particularly in people living with HIV, the population at greatest risk for development of active TB disease.

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Characterization of Mycobacterium tuberculosis-Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection.

Publications

Characterization of <i>Mycobacterium tuberculosis</i>-Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection.

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Dataset Information

Characterization of Mycobacterium tuberculosis-Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection.

Publications

Characterization of &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt;-Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection.

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OmicsDI is part of the ELIXIR infrastructure

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Characterization of <i>Mycobacterium tuberculosis</i>-Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection.