Zajac Allan J, Dye John M, Quinn Daniel G
Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois 60153, USA.
Virology. 2003 Jan 5;305(1):1-9. doi: 10.1006/viro.2002.1754.
We have investigated whether granzyme B (GzmB) is required for effective cytotoxic T lymphocyte (CTL) mediated control of lymphocytic choriomeningitis virus (LCMV) infection. Clearance of LCMV from tissues of GzmB-deficient (GzmB-) mice following intraperitoneal infection with LCMV was impaired compared with control mice; however, the virus was ultimately eliminated. The impaired clearance of LCMV in GzmB- mice was not due to a deficiency in the generation of LCMV-specific T cells. In addition, CTL from LCMV-infected GzmB- mice efficiently lysed virus-infected cells in vitro, but were deficient in their ability to induce rapid DNA fragmentation in target cells. We examined whether the development of protective immunity against intracranial (i.c.) rechallenge with LCMV was compromised in GzmB- mice. We found that clearance of LCMV from the brain following secondary i.c. infection also was slower in the absence of GzmB; however, the virus was ultimately eliminated and the mice survived. Our data indicate that clearance of LCMV is delayed in the absence of GzmB expression, but that other CTL effector molecules can compensate for the absence of this granule constituent in vivo.
我们研究了在细胞毒性T淋巴细胞（CTL）介导的对淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染的有效控制中，颗粒酶B（GzmB）是否是必需的。与对照小鼠相比，LCMV腹腔感染后，GzmB缺陷（GzmB-）小鼠组织中LCMV的清除受损；然而，病毒最终被清除。GzmB-小鼠中LCMV清除受损并非由于LCMV特异性T细胞生成不足。此外，来自LCMV感染的GzmB-小鼠的CTL在体外能有效裂解病毒感染的细胞，但诱导靶细胞快速DNA片段化的能力不足。我们研究了GzmB-小鼠对LCMV颅内（i.c.）再次攻击的保护性免疫发育是否受损。我们发现，在没有GzmB的情况下，二次i.c.感染后LCMV从脑中的清除也较慢；然而，病毒最终被清除，小鼠存活。我们的数据表明，在没有GzmB表达的情况下，LCMV的清除会延迟，但其他CTL效应分子可以在体内补偿这种颗粒成分的缺失。
