Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa.
J Immunol. 2022 Aug 1;209(3):446-455. doi: 10.4049/jimmunol.2200140. Epub 2022 Jul 1.
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 -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 -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 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. -specific IL-22 responses were markedly reduced (median, 0.08%) in individuals with TB disease and HIV coinfection compared with IFN-γ responses. -specific Th22 cells exhibited a distinct memory and activation phenotype compared with Th1 and Th17 cells. Furthermore, -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 -specific Th22 cells during HIV coinfection may contribute to increased risk of TB disease.
针对潜伏性结核感染或结核病患者（伴或不伴 HIV-1 感染），我们对 72 人外周血单个核细胞（PBMC）中的 - 特异性 Th22（及 Th1 和 Th17）细胞进行了鉴定，分析了其功能特性（IFN-γ、IL-22 和 IL-17 的产生）、记忆分化（CD45RA、CD27 和 CCR7）和激活特征（HLA-DR）。在潜伏性结核感染的 HIV 阴性个体中，我们检测到大量的 IFN-γ 产生 CD4 T 细胞（中位数，0.93%）和 IL-22 产生 CD4 T 细胞（中位数，0.46%）。IL-17 产生 CD4 T 细胞的频率较低，中位数为 0.06%。与先前的研究一致，IL-22 由 CD4 T 细胞的一个独特亚群产生，而不与 IL-17 共表达。与 IFN-γ 反应相比，HIV 合并结核病患者的 - 特异性 IL-22 反应明显降低（中位数，0.08%）。与 Th1 和 Th17 细胞相比，- 特异性 Th22 细胞具有独特的记忆和激活表型。此外，- 特异性 IL-22 由需要 TCR 参与的常规 CD4 T 细胞产生。总之，我们证实 Th22 细胞是人类针对结核分枝杆菌免疫反应的一部分。HIV 合并感染时 - 特异性 Th22 细胞的耗竭可能导致结核病发病风险增加。
