The role,of host CD4 T cells in the pathogenesis of the chronic graft-versus-host model of systemic lupus erythematosus
The role,of host CD4 T cells in the pathogenesis of the chronic graft-versus-host model of systemic lupus erythematosus
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DOI：
10.4049/jimmunol.174.12.7600
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发表时间：
2005-06-15
影响因子：
4.4
通讯作者：
Eisenberg, RA
中科院分区：
文献类型：
--
作者：
Choudhury, A;Maldonado, MA;Eisenberg, RA
系统性红斑狼疮的特征是产生自身抗体和肾小球肾炎。系统性红斑狼疮的小鼠慢性移植物抗宿主（cGVH）模型是通过外源 MHC II 类决定簇的同种异体识别诱导的。先前的研究表明，cGVH 无法在 CD4 敲除（CD4KO）小鼠中诱导。我们进一步探讨了宿主 CD4 T 细胞在此模型中的作用。我们的研究现在表明，CD4KO 小鼠的 B 细胞具有内在缺陷，导致它们无法对同种异体帮助做出反应。此外，CD4KO小鼠中的B细胞与同源C57BL/6 B细胞相比表现出表型差异，表明具有一定程度的体内激活以及具有边缘区B细胞表型的细胞数量增加。在 cGVH 开始时转移同基因 CD4 T 细胞并不能纠正这些 B 细胞异常；然而，如果在 B 细胞发育和成熟过程中转移 CD4 T 细胞，那么来自 CD4KO 小鼠的 B 细胞就获得了对 cGVH 做出反应的能力。这些研究清楚地表明，B 细胞需要在发育早期与 CD4 T 细胞共存，才能对同种激活信号完全敏感。
Systemic lupus erythematosus is characterized by production of autoantibodies and glomerulonephritis. The murine chronic graft-vs-host (cGVH) model of systemic lupus erythematosus is induced by allorecognition of foreign MHC class II determinants. Previous studies have shown that cGVH could not be induced in CD4 knockout (CD4KO) mice. We have further explored the role of host CD4 T cells in this model. Our studies now show that B cells in CD4KO mice have intrinsic defects that prevent them from responding to allohelp. In addition, B cells in CD4KO mice showed phenotypic differences compared with congeneic C57BL/6 B cells, indicating some degree of in vivo activation and increased numbers of cells bearing a marginal zone B cell phenotype. The transfer of syngeneic CD4 T cells at the time of initiation of cGVH did not correct these B cell abnormalities; however, if CD4 T cells were transferred during the development and maturation of B cells, then the B cells from CD4KO mice acquire the ability to respond in cGVH. These studies clearly indicate that B cells need to coexist with CD4 T cells early in their development to develop full susceptibility to alloactivation signals.