Scriba Thomas J, Kalsdorf Barbara, Abrahams Deborah-Ann, Isaacs Fatima, Hofmeister Jessica, Black Gillian, Hassan Hisham Y, Wilkinson Robert J, Walzl Gerhard, Gelderbloem Sebastian J, Mahomed Hassan, Hussey Gregory D, Hanekom Willem A
South African Tuberculosis Vaccine Initiative, Observatory, South Africa.
J Immunol. 2008 Feb 1;180(3):1962-70. doi: 10.4049/jimmunol.180.3.1962.
We investigated whether the proinflammatory T cell cytokines IL-17 and IL-22 are induced by human mycobacterial infection. Remarkably, >20% of specific cytokine-producing CD4(+) T cells in peripheral blood of healthy, mycobacteria-exposed adults expressed IL-17 or IL-22. Specific IL-17- and IL-22-producing CD4(+) T cells were distinct from each other and from Th1 cytokine-producing cells. These cells had phenotypic characteristics of long-lived central memory cells. In patients with tuberculosis disease, peripheral blood frequencies of these cells were reduced, whereas bronchoalveolar lavage fluid contained higher levels of IL-22 protein compared with healthy controls. IL-17 was not detected in this fluid, which may be due to suppression by Th1 cytokines, as PBMC IL-17 production was inhibited by IFN-gamma in vitro. However, Th1 cytokines had no effect on IL-22 production in vitro. Our results imply that the magnitude and complexity of the anti-mycobacterial immune response have historically been underestimated. IL-17- and IL-22-producing CD4(+) T cells may play important roles in the human immune response to mycobacteria.
我们研究了促炎性T细胞细胞因子IL-17和IL-22是否由人类分枝杆菌感染诱导产生。值得注意的是，在接触过分枝杆菌的健康成年人外周血中，超过20%产生特定细胞因子的CD4(+) T细胞表达了IL-17或IL-22。产生特异性IL-17和IL-22的CD4(+) T细胞彼此不同，也与产生Th1细胞因子的细胞不同。这些细胞具有长寿中枢记忆细胞的表型特征。在结核病患者中，这些细胞的外周血频率降低，而与健康对照相比，支气管肺泡灌洗液中IL-22蛋白水平更高。在该液体中未检测到IL-17，这可能是由于Th1细胞因子的抑制作用，因为体外PBMC的IL-17产生受到IFN-γ的抑制。然而，Th1细胞因子在体外对IL-22的产生没有影响。我们的结果表明，抗分枝杆菌免疫反应的强度和复杂性在历史上一直被低估。产生IL-17和IL-22的CD4(+) T细胞可能在人类对分枝杆菌的免疫反应中发挥重要作用。
