The natural history of disease expression in CD4 and CD8 gene-deleted New Zealand black (NZB) mice.
The natural history of disease expression in CD4 and CD8 gene-deleted New Zealand black (NZB) mice.
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CD4 和 CD8 基因缺失的新西兰黑 (NZB) 小鼠疾病表达的自然史。
DOI：
10.4049/jimmunol.157.6.2676
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发表时间：
1996
影响因子：
4.4
通讯作者：
M. Gershwin
中科院分区：
文献类型：
--
作者：
S. Chen;Y. Takeoka;Aftab A. Ansari;Richard L. Boyd;Dennis M. Klinman;M. Gershwin
以新西兰黑(NZB)小鼠为研究对象，以B6、CD8-/-、B6、CD8-/-、CD8-/-、NZB和B6野生型(Wt)小鼠为对照，对其表型和免疫学参数进行了研究，以确定CD8和CD8细胞系在NZB小鼠中的作用。这些研究表明，令人惊讶的是，许多异常并不是由于CD4+或CD8+细胞谱系，而是最有可能是由于非CD4+和-CD8+细胞谱系和/或背景基因。这些异常包括胸腺结构改变，MITS 33+髓质胸腺细胞染色减少，以及脾IgM分泌细胞频率增加。相反，CD4+或CD8+细胞的缺失似乎会对免疫功能产生不同的影响。CD8+细胞的缺失不影响自发产生的抗红细胞或抗DNA自身抗体的滴度。有趣的是，50%的NZB.CD4-/-小鼠体内含有抗红细胞免疫球蛋白G和抗单链DNA免疫球蛋白M自身抗体；即使没有检测到的CD4+细胞也是如此。这种CD4+细胞的缺失，虽然导致B6小鼠Th1和Th2亚群特征的原型细胞因子显著减少，但导致NZB.CD4-/-小鼠体内干扰素-γ显著增加，IL-4mRNA水平适度增加。这些数据表明，尽管非CD4+和-CD8+细胞谱系和NZB背景基因在自身免疫异常的发生中有显著影响，但CD4+细胞似乎在影响细胞因子环境方面发挥了主要作用，而CD8+细胞似乎发挥了次要作用。
CD4 and CD8 gene-deleted New Zealand black (NZB) mice and, as controls, B6.CD4 -/-, B6.CD8 -/-, NZB, and B6 wild-type (wt) mice were studied for phenotypic and immunologic parameters to determine the contribution of CD4 and CD8 cell lineages in NZB mice. These studies suggest surprisingly that a number of abnormalities are not due to either CD4+ or CD8+ cell lineages but rather are most likely due to non-CD4+ and -CD8+ cell lineages and/or background genes. Such abnormalities include altered thymic architecture, decreased staining of MITS 33+ medullary thymocytes, and an increased frequency of splenic IgM secretory cells. In contrast, deletion of either CD4+ or CD8+ cells appears to differentially influence immunologic function. Deletion of CD8+ cells did not influence titers of spontaneously occurring anti-erythrocyte or anti-DNA autoantibodies. interestingly, 50% of NZB.CD4 -/- mice contained levels of anti-erythrocyte IgG and anti-ssDNA IgM autoantibodies; even without detectable CD4+ cells. Such deletion of CD4+ cells, while leading to marked decreases in the prototype cytokines that characterize Th1 and Th2 subsets in B6 mice, led to a marked increase in IFN-gamma and a moderate increase in IL-4 mRNA levels in NZB.CD4 -/- mice. These data suggest that whereas non-CD4+ and -CD8+ cell lineages and NZB background genes have a marked influence in the development of autoimmune abnormalities, CD4+ cells appear to play a major role in influencing the cytokine environment, whereas CD8+ cells appear to play a minor role.