Soboslay P T, Lüder C G, Riesch S, Geiger S M, Banla M, Batchassi E, Stadler A, Schulz-Key H
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
Immunology. 1999 Jun;97(2):219-25. doi: 10.1046/j.1365-2567.1999.00018.x.
The present study investigated in vitro the regulatory effects of T helper 1 (Th1)-type (interferon-gamma, IFN-gamma; interleukin-12, IL-12) and Th2-type cytokines (IL-10, IL-13) on Onchocerca volvulus-specific cellular reactivity in onchocerciasis patients, and in exposed endemic control individuals presenting no clinical and parasitological signs of disease. In both patients and controls, addition of IL-10 dose-dependently depressed O. volvulus antigen (OvAg)-specific cellular proliferation, and peripheral blood mononuclear cells (PBMC) from patients who were more sensitive to the suppressive effect of IL-10 than those from endemic controls. However, neutralization of IL-10 by specific antibody did not reverse cellular hyporesponsiveness. In contrast to the inhibitory effects of IL-10, exogenous IL-12 and IL-13 augmented PBMC proliferative responses to OvAg both in patients and controls (P<0. 01) and neutralizing of IL-12 or IL-13 significantly decreased OvAg-specific proliferation in both groups. Exogenous IFN-gamma did not activate OvAg-specific proliferative responses in patients, but anti-IFN-gamma antibodies abolished cellular reactivity to OvAg. Antibody to IL-10 increased (P<0.05) OvAg-specific production of IL-5, IL-12 and IFN-gamma, and inversely, anti-IFN-gamma enhanced IL-10 (in patients only) and IL-5 and IL-13 in both patients and controls. Neutralization of IL-12 activated OvAg-specific production of IL-10, IL-2 and IFN-gamma. In conclusion, despite of an overproduction of IL-10, which suppressed cellular reactivity in patients and control individuals, OvAg-specific cellular responses were activated in vitro by exogenous supplementation with IL-12 and IL-13, and cytokine neutralization experiments confirmed that distinct type 1 and type 2 T helper cytokines cross-regulate expression and magnitude of O. volvulus-specific cellular responsiveness in humans.
本研究在体外调查了辅助性T细胞1（Th1）型细胞因子（干扰素-γ，IFN-γ；白细胞介素-12，IL-12）和Th2型细胞因子（IL-10、IL-13）对盘尾丝虫病患者以及未出现疾病临床和寄生虫学体征的暴露流行区对照个体中盘尾丝虫特异性细胞反应性的调节作用。在患者和对照个体中，添加IL-10均剂量依赖性地抑制盘尾丝虫抗原（OvAg）特异性细胞增殖，且患者外周血单个核细胞（PBMC）比流行区对照个体的PBMC对IL-10的抑制作用更敏感。然而，用特异性抗体中和IL-10并未逆转细胞低反应性。与IL-10的抑制作用相反，外源性IL-12和IL-13增强了患者和对照个体中PBMC对OvAg的增殖反应（P<0.01），中和IL-12或IL-13均显著降低两组中OvAg特异性增殖。外源性IFN-γ未激活患者中OvAg特异性增殖反应，但抗IFN-γ抗体消除了细胞对OvAg的反应性。抗IL-10抗体增加了（P<0.05）OvAg特异性IL-5、IL-12和IFN-γ的产生，相反，抗IFN-γ增强了IL-10（仅在患者中）以及患者和对照个体中IL-5和IL-13的产生。中和IL-12激活了OvAg特异性IL-10、IL-2和IFN-γ的产生。总之，尽管患者和对照个体中IL-10产生过多并抑制了细胞反应性，但通过外源性补充IL-12和IL-13在体外激活了OvAg特异性细胞反应，细胞因子中和实验证实，不同的1型和2型辅助性T细胞因子交叉调节人类中盘尾丝虫特异性细胞反应性的表达和强度。
