The pathogenesis of autoimmunity in New Zealand mice.
The pathogenesis of autoimmunity in New Zealand mice.
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DOI：
10.1016/0049-0172(80)90004-9
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发表时间：
1990
影响因子：
5
通讯作者：
S. Yoshida;J. J. Castles-J.;M. E. Gershwin
中科院分区：
文献类型：
--
作者：
S. Yoshida;J. J. Castles-J.;M. E. Gershwin
在过去的几年里，新西兰小鼠研究领域的信息爆炸。这反映了细胞免疫学和淋巴细胞生物学方面的知识和技术的普遍增长。在许多具体领域的持续研究有望扩大这一不断增长的数据库。过去记录的新西兰小鼠CMI的许多异常目前正在分析细胞协同作用，而不是简单的效应机制。这样的分析表明，老年新西兰小鼠中CMI的损伤更具选择性，而不是一般性。类似地，正在探索由NZ小鼠表达的同种异体H-2相同的细胞毒活性及其与自身免疫性疾病的相关性。在新西兰小鼠的抑制功能领域，在对现有信息进行充分解释之前，必须实现抑制测定的持续改进和标准化。老年新西兰小鼠的抑制活性被描述为抑郁，正常和升高。这是一个非常令人感兴趣的领域。虽然主要的病因学意义的T细胞调节缺陷，目前正在最小化，其可能的次要作用，在新西兰小鼠的自身免疫性疾病的发病机制正在调查。最近发现的一个显着的B细胞异常，目前从出生在所有SLE倾向的小鼠品系增加的可能性，内在的B细胞过度活跃是一个主要的病因因素，在小鼠自身免疫。许多实验室正在对在新西兰小鼠中观察到的IgM分泌过多和B细胞集落形成单位发生率增加进行进一步的遗传分析。类似地，对（CBA/N × NZB）杂种的持续评价有望具有启发性，特别是在NZB背景下开发具有CBZ/NX染色体的同源小鼠。此外，H-2同源NZB菌株和免疫球蛋白同种异型同源NZB菌株的开发正在进行中。这些菌株将提供有关MHC和VH区在自身免疫发病机制中可能作用的信息。NZB.ch同源株已被证明具有很大的价值。先天性免疫突变NZ小鼠的继续开发和进一步表征已经并将继续有助于阐明这些动物中自身免疫发展的机制。虽然新西兰小鼠表达多种宿主-病毒相互作用，但最近的遗传分析表明，病毒感染不是新西兰小鼠自身免疫性疾病的主要病原体。已在NZ小鼠中描述了明确的临床实体和一系列异常。目前的目标是通过对这一重要的人类自身免疫性疾病动物模型进行持续的免疫学和遗传学分析来确定自身免疫的细胞基础。
In the past few years there has been an explosion of information in the area of NZ mouse research. This has reflected a general increase in knowledge and technology in cellular immunology and lymphocyte biology. Continuing research in many specific areas promises to expand this increasing data base. The numerous abnormalities of CMI in NZ mice chronicled in the past are currently being analyzed in terms of cell synergism rather than as simple effector mechanisms. Such analysis is indicating more selective rather than general impairment of CMI in aging NZ mice. Similarly, the allogeneic H-2 identical cytotoxic activity expressed by NZ mice and its relevance to autoimmune disease are being explored. In the area of suppressor functions in NZ mice, continued refinement and standardization of suppressor assays must be achieved before adequate interpretation of the present information can be made. Suppressor activity in aging NZ mice has been described as depressed, normal, and elevated. This is an area of acute interest. While the primary etiologic significance of T cell regulatory defects is currently being minimized, their possible secondary role in pathogenesis of autoimmune disease in NZ mice is being investigated.The recent discovery of a significant B cell abnormality present from birth in all SLE-prone murine strains has increased the probability that intrinsic B cell hyperactivity is a primary etiologic factor in murine autoimmunity. The hypersecretion of IgM and the increased incidence of B cell colony-forming units observed in NZ mice is being subjected to further genetic analysis in many laboratories. Similarly, the continued evaluation of the (CBA/N × NZB) hybrid promises to be enlightening, particularly the development of congeneic mice with the CBZ/N X chromosome on the NZB background. In addition, the development of H-2 congeneic NZB strains and immunoglobulin allotype congeneic NZB strains are proceeding. These strains will provide information on the possible roles of MHC and VHregions in autoimmune pathogenesis. The NZB.ch congeneic strain has already proven to be of great value.The continued development and further characterization of congenitally immunologic mutant NZ mice has been and will continue to be useful in elucidating the mechanism of autoimmune development in these animals. While NZ mice express a variety of host-viral interactions, recent genetic analysis suggests that viral infection is not a primary etiologic agent in the autoimmune disease of NZ mice. A well-defined clinical entity and a range of abnormalities have been delineated in NZ mice. The present goal is to define the cellular basis of autoimmunity through continued immunologic and genetic analysis of this important animal model of human autoimmune disease.