Okada H, Sato T A, Katayama A, Higuchi K, Shichijo K, Tsuchiya T, Takayama N, Takeuchi Y, Abe T, Okabe N, Tashiro M
Department of Viral Diseases and Vaccine Control, National Institute of Infectious Diseases, Musashi-Murayama, Tokyo, Japan.
Arch Virol. 2001;146(5):859-74. doi: 10.1007/s007050170121.
Measles virus infection induces a profound immunosuppression. We analyzed in a time-dependent manner peripheral bloods of one to two-year-old children immunized with live attenuated measles vaccines, compared with age-matched measles patients, for immunosuppression. In contrast to transient severe lymphopenia with measles patients, primarily due to extensive apoptosis of a broad spectrum of uninfected lymphocytes, neither apoptosis nor lymphopenia occurred with measles vaccine recipients. Increase in number and activation of NK cells, which might compensate for the lymphopenia in measles patients, were not found with the vaccinees. While cell surface expression of apoptosis-related molecules such as TNF-related apoptosis-inducing ligand (TRAIL), TRAIL-receptors, CD95(Fas) and Fas-ligand, and plasma interferon-gamma were increased for measles patients, they remained unchanged after vaccination. Plasma interleukin (IL)-18, which is responsible for inducing apoptosis in several infectious diseases, was increased predominantly with measles patients, whereas the increase remained marginal with the vaccinees. IL-10 was elevated transiently in both measles patients and vaccinees. Decrease in plasma IL-12, which is often correlated with T cell suppression, was not found for both cases. Serum IgM and IgG antibodies to measles virus were induced at lower titers in the vaccinees than measles patients. These results indicate that in contrast to wild-type measles virus, live measles vaccines hardly provoked host cytokine responses that lead to apoptotic cytolysis of uninfected lymphocytes, lymphopenia and immunosuppression, and thereby induced weaker immune responses to the virus.
麻疹病毒感染会引发严重的免疫抑制。我们以时间依赖的方式,对一到两岁接种减毒活麻疹疫苗的儿童外周血进行分析,并与年龄匹配的麻疹患者外周血作比较,以研究免疫抑制情况。与麻疹患者出现的短暂性严重淋巴细胞减少不同,后者主要是由于多种未感染淋巴细胞的广泛凋亡所致,而接种麻疹疫苗的儿童既未出现凋亡现象,也未出现淋巴细胞减少。接种疫苗者未发现自然杀伤细胞(NK细胞)数量增加及活化,而这可能会弥补麻疹患者的淋巴细胞减少。麻疹患者细胞表面凋亡相关分子如肿瘤坏死因子相关凋亡诱导配体(TRAIL)、TRAIL受体、CD95(Fas)和Fas配体以及血浆干扰素-γ表达增加,但接种疫苗后这些分子保持不变。血浆白细胞介素(IL)-18在多种传染病中可诱导凋亡,主要在麻疹患者中升高,而接种疫苗者的升高幅度较小。IL-10在麻疹患者和接种疫苗者中均短暂升高。两种情况下均未发现血浆IL-12降低,IL-12降低通常与T细胞抑制相关。接种疫苗者体内针对麻疹病毒的血清IgM和IgG抗体滴度低于麻疹患者。这些结果表明,与野生型麻疹病毒不同,减毒活麻疹疫苗几乎不会引发导致未感染淋巴细胞凋亡性细胞溶解、淋巴细胞减少和免疫抑制的宿主细胞因子反应,因此对病毒诱导的免疫反应较弱。