Characterization of Mycobacterium tuberculosis–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 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.