Szkaradkiewicz Andrzej, Jopek Aleksandra, Wysocki Jacek, Grzymislawski Marian, Malecka Ilona, Woźniak Aldona
University of Medical Sciences in Poznań, Wieniawskiego 3, 61-712 Poznań, Poland.
Virus Res. 2003 Nov;97(2):127-33. doi: 10.1016/j.virusres.2003.08.013.
In the presented studies HBcAg-specific cytokine production (IFN-gamma, IL-2, IL-4, IL-5 and IL-10) was evaluated, by Th lymphocytes isolated from peripheral blood of children with acute or chronic B hepatitis. Moreover, effect of IL-10 neutralization was examined on HBcAg-induced secretory response of Th lymphocytes obtained from children with chronic B hepatitis. The studies were performed on 12 children with acute self-limited B hepatitis and 20 children with chronic active B hepatitis. CD4 T cells were isolated from peripheral blood of the patients, cultured for 48h in presence of rHBcAg or in its absence (control). Production of studied cytokines was monitored using ELISPOT and ELISE assays. The course of acute self-limited B hepatitis was associated with preferential Th1-type response, manifested by elevated production of IFN-gamma and IL-2. On the other hand, in chronic B hepatitis a diminished response to HBcAg of both Th1 and Th2 types was disclosed, characterized by very low secretion of IFN-gamma, IL-2, IL-4 and IL-5. In parallel, preferential antigen-specific production of IL-10 was noted and its suppressive effect on HBcAg-induced response of Th1 cells. The results permitted to conclude that in children with acute self-limited B hepatitis preferential HBcAg-specific activation of Th1 lymphocytes may be of significance for efficient anti-HBV immune response. On the other hand, development of chronic B infection in children seems to be determined by disturbed HBcAg-specific functions of both Th1 and Th2 cells whereas activity of the disease may be controlled by anti-inflammatory response of antigen-presenting cells and/or of regulatory CD4 T lymphocytes, involving IL-10 production.
在本研究中,评估了从急性或慢性乙型肝炎患儿外周血中分离出的Th淋巴细胞产生的HBcAg特异性细胞因子(IFN-γ、IL-2、IL-4、IL-5和IL-10)。此外,还检测了IL-10中和对慢性乙型肝炎患儿Th淋巴细胞HBcAg诱导的分泌反应的影响。研究对象为12例急性自限性乙型肝炎患儿和20例慢性活动性乙型肝炎患儿。从患者外周血中分离出CD4 T细胞,在有或无重组HBcAg(rHBcAg)的情况下培养48小时。使用ELISPOT和ELISA检测法监测所研究细胞因子的产生。急性自限性乙型肝炎的病程与优先的Th1型反应相关,表现为IFN-γ和IL-2产生增加。另一方面,在慢性乙型肝炎中,发现Th1和Th2型对HBcAg的反应均减弱,其特征是IFN-γ、IL-2、IL-4和IL-5的分泌非常低。同时,观察到优先的抗原特异性IL-10产生及其对Th1细胞HBcAg诱导反应的抑制作用。结果表明,在急性自限性乙型肝炎患儿中,优先的HBcAg特异性Th1淋巴细胞激活可能对有效的抗HBV免疫反应具有重要意义。另一方面,儿童慢性乙型肝炎感染的发展似乎取决于Th1和Th2细胞HBcAg特异性功能的紊乱,而疾病的活动可能由抗原呈递细胞和/或调节性CD4 T淋巴细胞的抗炎反应控制,涉及IL-10的产生。