M. tuberculosis antigen-responsive IL17(+) CD4 T cells are disproportionately spared in ART-suppressed HIV

BACKGROUND. Interleukin 17 producing CD4 T cells contribute to control of Mycobacterium tuberculosis (Mtb) infection in humans; whether infection with Human Immunodeficiency Virus (HIV) disproportionately affects distinct Th17 cell subsets that respond to Mtb are incompletely defined. METHODS. We performed high-definition characterization of circulating Mtb-specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity in plasma by LC/MS and tested the hypothesis that tryptophan catabolism influences Th17 cell differentiation in this context. RESULTS. We identified two categories of Th17 cells: T(H)17 (CD4(+)Vα7.2(−)CD161(+)CD26(+)) and T17 (CD4(+)Vα7.2(−)CCR6(+)CXCR3(−)) cells that were disproportionately reduced in LTBI with HIV-ART, yet Mtb-responsive IL17-producing CD4 T cells were preserved; we found that IL17-producing CD4 T cells dominate the response to Mtb antigen but not CMV antigen or staphylococcal enterotoxin B (SEB); and tryptophan catabolism negatively correlates with T(H)17 and T1T17 but not T17 cell frequencies. CONCLUSIONS. We found differential effects of ART-suppressed HIV on distinct categories of Th17 cells, that IL17-producing CD4 T cells dominate responses to Mtb but not CMV antigen or SEB, and that kynurenine pathway activity is associated with selective decreases of circulating Th17 cells that may contribute to tuberculosis immunity.