High-parameter phenotypic characterization reveals a subset of human Th17 cells that preferentially produce IL17 against antigen.

BACKGROUND

Interleukin 17 producing CD4 T cells contribute to the control of infection in humans; whether infection with Human Immunodeficiency Virus (HIV) disproportionately affects distinct Th17 cell subsets that respond to is incompletely defined.

METHODS

We performed high-definition characterization of circulating -specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity by LC/MS on plasma and tested the hypothesis that tryptophan catabolism influences Th17 cell frequencies in this context.

RESULTS

We identified two subsets of Th17 cells: subset 1 defined as CD4Vα7.2CD161CD26 and subset 2 defined as CD4Vα7.2CCR6CXCR3 cells of which subset 1 was significantly reduced in LTBI with HIV-ART, yet -responsive IL17-producing CD4 T cells were preserved; we found that IL17-producing CD4 T cells dominate the response to antigen but not CMV antigen or staphylococcal enterotoxin B (SEB); and tryptophan catabolism negatively correlates with both subset 1 and subset 2 Th17 cell frequencies.

CONCLUSIONS

We found differential effects of ART-suppressed HIV on distinct subsets of Th17 cells, that IL17-producing CD4 T cells dominate responses to 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.