Thomas Sunil, Kolumam Ganesh A, Murali-Krishna Kaja
Department of Immunology and Washington National Primate Center, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA.
J Immunol. 2007 May 1;178(9):5802-11. doi: 10.4049/jimmunol.178.9.5802.
Professional APCs of hemopoietic-origin prime pathogen-specific naive CD8 T cells. The primed CD8 T cells can encounter Ag on infected nonhemopoietic cell types. Whether these nonhemopoietic interactions perpetuate effector T cell expansion remains unknown. We addressed this question in vivo, using four viral and bacterial pathogens, by comparing expansion of effector CD8 T cells in bone marrow chimeric mice expressing restricting MHC on all cell types vs mice that specifically lack restricting MHC on nonhemopoietic cell types or radiation-sensitive hemopoietic cell types. Absence of Ag presentation by nonhemopoietic cell types allowed priming of naive CD8 T cells in all four infection models tested, but diminished their sustained expansion by approximately 10-fold during lymphocytic choriomeningitis virus and by < or =2-fold during vaccinia virus, vesicular stomatitis virus, or Listeria monocytogenes infections. Absence of Ag presentation by a majority (>99%) of hemopoietic cells surprisingly also allowed initial priming of naive CD8 T cells in all the four infection models, albeit with delayed kinetics, but the sustained expansion of these primed CD8 T cells was markedly evident only during lymphocytic choriomeningitis virus, but not during vaccinia virus, vesicular stomatitis virus, or L. monocytogenes. Thus, infected nonhemopoietic cells can amplify effector CD8 T cell expansion during infection, but the extent to which they can amplify is determined by the pathogen. Further understanding of mechanisms by which pathogens differentially affect the ability of nonhemopoietic cell types to contribute to T cell expansion, how these processes alter during acute vs chronic phase of infections, and how these processes influence the quality and quantity of memory cells will have implications for rational vaccine design.
造血来源的专业抗原呈递细胞（APCs）启动病原体特异性的初始CD8 T细胞。启动后的CD8 T细胞可在受感染的非造血细胞类型上遇到抗原。这些非造血细胞间的相互作用是否能使效应T细胞持续扩增仍不清楚。我们在体内使用四种病毒和细菌病原体来解决这个问题，通过比较在所有细胞类型上表达限制性MHC的骨髓嵌合小鼠与在非造血细胞类型或辐射敏感造血细胞类型上特异性缺乏限制性MHC的小鼠中效应CD8 T细胞的扩增情况。在所有四种测试的感染模型中，非造血细胞类型缺乏抗原呈递允许初始CD8 T细胞启动，但在淋巴细胞性脉络丛脑膜炎病毒感染期间，其持续扩增减少了约10倍，在痘苗病毒、水疱性口炎病毒或单核细胞增生李斯特菌感染期间减少了≤2倍。令人惊讶的是，大多数（>99%）造血细胞缺乏抗原呈递在所有四种感染模型中也允许初始CD8 T细胞启动，尽管动力学延迟，但这些启动后的CD8 T细胞的持续扩增仅在淋巴细胞性脉络丛脑膜炎病毒感染期间明显，而在痘苗病毒、水疱性口炎病毒或单核细胞增生李斯特菌感染期间则不明显。因此，受感染的非造血细胞可在感染期间扩增效应CD8 T细胞，但它们的扩增程度由病原体决定。进一步了解病原体如何差异影响非造血细胞类型促进T细胞扩增的能力、这些过程在感染急性期与慢性期如何变化以及这些过程如何影响记忆细胞的质量和数量，将对合理疫苗设计具有重要意义。
