Alber D G, Greensill J, Killington R A, Stokes A
Department of Microbiology, University of Leeds.
Res Vet Sci. 1995 Nov;59(3):205-13. doi: 10.1016/0034-5288(95)90003-9.
The suitability of C3H (H-2k) and BALB/c (H-2d) mice for use as small animal models to study immunity to EHV-1 was assessed. An in vitro T cell response mediated by both CD4+ and CD8+ T cells was detected both during the acute phase of infection and after challenge with a second dose of EHV-1 at two months in lymphocyte populations taken from the spleens of both types of mouse. The responses were apparent until at least 61 days after the primary inoculation. After challenge, T cells from mice previously infected with EHV-1 responded by as early as day 3 after infection and higher levels of T cell proliferation were reached than in mice undergoing a primary infection. Immunological cross-reactivity with the closely related virus, EHV-4 was detected and some activity against herpes simplex virus type-1 (HSV-1) was observed during the acute phase of infection. T cell responses were detected in the draining cervical lymph nodes but not in the inguinal lymph nodes of the mice and these were the primary sites of T cell activation. Complement-dependent virus neutralising antibodies were present by day 8 after infection. These antibodies were also able to lyse EHV-1 infected target cells in vitro. Complement-independent virus neutralising antibodies were found before challenge only in C3H mice. The clinical signs and duration of virus shedding were reduced after challenge. The time course of the appearance of the different immune effector mechanisms is discussed in relation to the clearance of virus from the infected mice. The results suggest that C3H mice provide a better model in which to study potential vaccine candidates against EHV-1 infections of the horse than BALB/c mice.
评估了C3H(H-2k)和BALB/c(H-2d)小鼠作为研究对EHV-1免疫的小动物模型的适用性。在感染急性期以及在两个月后用第二剂EHV-1攻击后,从两种小鼠脾脏获取的淋巴细胞群体中均检测到由CD4+和CD8+ T细胞介导的体外T细胞应答。这些应答至少在初次接种后61天仍然明显。攻击后,先前感染EHV-1的小鼠的T细胞最早在感染后第3天作出反应,并且达到的T细胞增殖水平高于初次感染的小鼠。在感染急性期检测到与密切相关的病毒EHV-4的免疫交叉反应性,并观察到对1型单纯疱疹病毒(HSV-1)的一些活性。在小鼠引流的颈部淋巴结中检测到T细胞应答,但在腹股沟淋巴结中未检测到,并且这些是T细胞活化的主要部位。感染后第8天出现补体依赖性病毒中和抗体。这些抗体在体外也能够裂解EHV-1感染的靶细胞。仅在C3H小鼠中在攻击前发现非补体依赖性病毒中和抗体。攻击后临床症状和病毒脱落持续时间缩短。讨论了不同免疫效应机制出现的时间进程与从感染小鼠清除病毒的关系。结果表明,与BALB/c小鼠相比,C3H小鼠为研究针对马EHV-1感染的潜在候选疫苗提供了更好的模型。