AUTHOR=Ogongo Paul , Tran Anthony , Marzan Florence , Gingrich David , Krone Melissa , Aweeka Francesca , Lindestam Arlehamn Cecilia S. , Martin Jeffrey N. , Deeks Steven G. , Hunt Peter W. , Ernst Joel D. 

TITLE=High-parameter phenotypic characterization reveals a subset of human Th17 cells that preferentially produce IL-17 against M. tuberculosis antigen

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1378040

DOI=10.3389/fimmu.2024.1378040

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Interleukin-17–producing CD4 T cells contribute to the control of <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) infection in humans; whether infection with human immunodeficiency virus (HIV) disproportionately affects distinct Th17-cell subsets that respond to <italic>Mtb</italic> is incompletely defined.</p></sec><sec><title>Methods</title><p>We performed high-definition characterization of circulating <italic>Mtb</italic>-specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity by liquid chromatography-mass spectrometry (LC/MS) on plasma and tested the hypothesis that tryptophan catabolism influences Th17-cell frequencies in this context.</p></sec><sec><title>Results</title><p>We identified two subsets of Th17 cells: subset 1 defined as CD4<sup>+</sup>Vα7.2<sup>−</sup>CD161<sup>+</sup>CD26<sup>+</sup>and subset 2 defined as CD4<sup>+</sup>Vα7.2<sup>−</sup>CCR6<sup>+</sup>CXCR3<sup>−</sup>cells of which subset 1 was significantly reduced in latent tuberculosis infection (LTBI) with HIV-ART, yet <italic>Mtb</italic>-responsive IL-17–producing CD4 T cells were preserved; we found that IL-17–producing CD4 T cells dominate the response to <italic>Mtb</italic> antigen but not cytomegalovirus (CMV) antigen or staphylococcal enterotoxin B (SEB), and tryptophan catabolism negatively correlates with both subset 1 and subset 2 Th17-cell frequencies.</p></sec><sec><title>Conclusions</title><p>We found differential effects of ART-suppressed HIV on distinct subsets of Th17 cells, that IL-17–producing CD4 T cells dominate responses to <italic>Mtb</italic> but not CMV antigen or SEB, and that kynurenine pathway activity is associated with decreases of circulating Th17 cells that may contribute to tuberculosis immunity.</p></sec>