Choudhury Arpita, Maldonado Michael A, Cohen Philip L, Eisenberg Robert A
Department of Medicine, Division of Rheumatology, University of Pennsylvania, and Veterans Affairs Medical Center, Philadelphia, PA 19104, USA.
J Immunol. 2005 Jun 15;174(12):7600-9. doi: 10.4049/jimmunol.174.12.7600.
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.
系统性红斑狼疮的特征是自身抗体的产生和肾小球肾炎。系统性红斑狼疮的小鼠慢性移植物抗宿主（cGVH）模型是由对外来主要组织相容性复合体（MHC）II类决定簇的同种异体识别诱导产生的。先前的研究表明，在CD4基因敲除（CD4KO）小鼠中无法诱导cGVH。我们进一步探讨了宿主CD4 T细胞在该模型中的作用。我们现在的研究表明，CD4KO小鼠中的B细胞存在内在缺陷，使其无法对同种异体辅助作出反应。此外，与同基因C57BL/6 B细胞相比，CD4KO小鼠中的B细胞表现出表型差异，表明存在一定程度的体内活化以及具有边缘区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细胞就会获得在cGVH中作出反应的能力。这些研究清楚地表明，B细胞在其发育早期需要与CD4 T细胞共存，以发展出对同种异体激活信号的完全易感性。
