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 (Mtb)-specific Th22 (and Th1 and Th17) cells in 72 individuals with latent tuberculosis infection (LTBI) or TB disease, with and without human immunodeficiency virus (HIV)-1 infection. We investigated the functional properties (IFN-gamma;, IL-22 and IL-17 production), memory differentiation (CD45RA, CD27 and CCR7) and activation profile (HLA-DR) of Mtb-specific CD4+ T cells. In HIV-uninfected individuals with LTBI, we detected abundant IFN-gamma; producing CD4+ T cells (median: 0.93%) and IL-22-producing CD4+ T cells (median: 0.46%) in response to Mtb. 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 co-expressed with IL-17. Mtb-specific IL-22 responses were markedly reduced (median: 0.08%) in individuals with TB disease and HIV co-infection compared to IFN-gamma; responses. Mtb-specific Th22 cells exhibited a distinct memory and activation phenotype compared to Th1 and Th17 cells. Furthermore, Mtb-specific IL-22 was produced by conventional CD4+ T cells that required T cell receptor (TCR) engagement. In conclusion, we confirm that Th22 cells contribute substantially to the immune response to TB. Depletion of Mtb-specific Th22 cells during HIV co-infection may contribute to increased risk of TB disease.

中文翻译：

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结核分枝杆菌特异性Th22细胞的表征以及结核病和HIV合并感染的影响

高效结核病疫苗的开发可能取决于我们对构成结核病保护性免疫应答的理解。越来越多的证据表明，产生IL-22（称为Th22细胞的不同子集）的CD4 + T细胞可能有助于抵抗结核病。因此，我们表征了72例结核分枝杆菌（Mtb）特异的Th22（以及Th1和Th17）细胞的潜伏性结核感染（LTBI）或结核病，有无人类免疫缺陷病毒（HIV）-1感染。我们研究了功能特性（IFN-γ； IL-22和IL-17的产生），记忆分化（CD45RA，CD27和CCR7）和Mtb特异性CD4 + T细胞的激活特征（HLA-DR）。在未感染HIV的LTBI患者中，我们检测到大量的IFN-γ。产生CD4 + T细胞（中位数：0。93％）和产生IL-22的CD4 + T细胞（中位数：0.46％）对Mtb的反应。产生IL-17的CD4 + T细胞的频率低得多，中位数为0.06％。与以前的研究一致，IL-22是由CD4 + T细胞的一个独特子集产生的，与IL-17不共表达。与IFN-γ相比，结核病和HIV合并感染患者的Mtb特异性IL-22反应显着降低（中位数：0.08％）。回应。与Th1和Th17细胞相比，Mtb特异性Th22细胞表现出独特的记忆和激活表型。此外，Mtb特异性IL-22由需要T细胞受体（TCR）参与的常规CD4 + T细胞产生。总之，我们确认Th22细胞在很大程度上促进了针对TB的免疫反应。