Evans C F, Rall G F, Killeen N, Littman D, Oldstone M B
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
J Immunol. 1993 Dec 1;151(11):6259-64.
The major host response to many viral infections is the generation of virus-specific CTL. Many protein molecules on the surfaces of both CTL and target cells interact to mediate adhesion of the cells and generate signals that lead to T cell activation and proliferation of virus-specific CTL that then mediate lysis of infected cells. One such protein, CD2, has been shown to increase the binding affinity of CTL to infected cells, and, in addition, enhance CTL activation signals. To determine whether virus-specific CTL could be generated in the absence of CD2, mice lacking a functional CD2 gene were infected with lymphocytic choriomeningitis virus (LCMV), and the responses to the virus were monitored. CD2-deficient mice infected intracerebrally with LCMV died as a consequence of CTL-mediated choriomeningitis, similar to control littermates. Additionally, CD2-deficient mice inoculated i.p. with LCMV cleared the infection by 2 wk postinfection, as did control mice. Viral clearance in these mice was shown to be due to the generation of a vigorous virus-specific MHC-restricted CTL response. Finally, to determine whether CD2 is essential for the generation of memory CTL, we examined the ability of CD2-deficient mice to generate memory CTL to LCMV and found normal memory CTL responses. Our results indicate that CD2 is not required for the generation of an LCMV-specific CTL response in vivo, nor is CD2 required for the maintenance or activation of memory CTL.
机体对许多病毒感染的主要宿主反应是产生病毒特异性细胞毒性T淋巴细胞(CTL)。CTL和靶细胞表面的许多蛋白质分子相互作用,介导细胞黏附并产生信号,导致T细胞活化以及病毒特异性CTL增殖,进而介导受感染细胞的裂解。其中一种蛋白质,即CD2,已被证明可增加CTL与受感染细胞的结合亲和力,此外,还能增强CTL活化信号。为了确定在缺乏CD2的情况下是否能产生病毒特异性CTL,将缺乏功能性CD2基因的小鼠感染淋巴细胞性脉络丛脑膜炎病毒(LCMV),并监测其对该病毒的反应。与对照同窝小鼠相似,经脑内感染LCMV的CD2缺陷小鼠因CTL介导的脉络丛脑膜炎而死亡。此外,经腹腔接种LCMV的CD2缺陷小鼠在感染后2周清除了感染,对照小鼠也是如此。这些小鼠的病毒清除被证明是由于产生了强烈的病毒特异性MHC限制性CTL反应。最后,为了确定CD2对于记忆性CTL的产生是否必不可少,我们检测了CD2缺陷小鼠产生针对LCMV的记忆性CTL的能力,发现其记忆性CTL反应正常。我们的结果表明,在体内产生LCMV特异性CTL反应不需要CD2,维持或激活记忆性CTL也不需要CD2。