Byrom B, Obwolo M, Barbet A F, Mahan S M
UF/USAID/SADC Heartwater Research Project, Central Veterinary Diagnostic and Research Laboratory, Harare, Zimbabwe.
J Parasitol. 2000 Oct;86(5):983-92. doi: 10.1645/0022-3395(2000)086[0983:APTTIR]2.0.CO;2.
Immune responses to Cowdria ruminantium, an intracellular organism that causes heartwater in domestic ruminants, were characterized in a DBA/2 mouse model. Immunity induced by infection and treatment was adoptively transferable by splenocytes and could be abrogated by in vivo depletion of T cells but not by inhibition of nitric oxide synthase using NG-monomethyl-L-arginine. IgG2a and IgG2b C. ruminantium-specific responses were detected in immune mice. Culture supernatants of splenocytes from immune DBA/2 mice, which were stimulated with crude C. ruminantium antigens or recombinant major antigenic proteins 1 or 2, contained significant levels of interferon (IFN)-gamma and interleukin (IL)-6, but insignificant levels of IL-1alpha, IL-2, IL-4, IL-5, IL-10, IL-12, tumor necrosis factor-alpha (TNF), and nitric oxide. A similar response was detected during primary infection, although IFN-gamma levels decreased significantly during clinical illness and then increased following natural or antibiotic-aided recovery. These data support the conclusion that protective immunity to C. ruminantium in DBA/2 mice is mediated by T cells and is associated with a polarized T helper 1 type of immune response. This murine model could be utilized to screen for protective C. ruminantium antigens that provoke Th1 type immune responses and for evaluation of these antigens in recombinant vaccines against heartwater.
在DBA/2小鼠模型中,对引起家畜反刍动物心水病的细胞内生物——反刍兽考德里氏体的免疫反应进行了表征。感染和治疗诱导的免疫力可通过脾细胞进行过继转移,并且可通过体内T细胞耗竭消除,但不能通过使用NG-单甲基-L-精氨酸抑制一氧化氮合酶来消除。在免疫小鼠中检测到了IgG2a和IgG2b反刍兽考德里氏体特异性反应。用粗制反刍兽考德里氏体抗原或重组主要抗原蛋白1或2刺激的免疫DBA/2小鼠脾细胞培养上清液中,含有显著水平的干扰素(IFN)-γ和白细胞介素(IL)-6,但IL-1α、IL-2、IL-4、IL-5、IL-10、IL-12、肿瘤坏死因子-α(TNF)和一氧化氮水平不显著。在初次感染期间检测到类似反应,尽管在临床疾病期间IFN-γ水平显著下降,然后在自然恢复或抗生素辅助恢复后升高。这些数据支持以下结论:DBA/2小鼠对反刍兽考德里氏体的保护性免疫由T细胞介导,并与极化的T辅助1型免疫反应相关。该小鼠模型可用于筛选引发Th1型免疫反应的保护性反刍兽考德里氏体抗原,并用于评估这些抗原在抗心水病重组疫苗中的作用。