Weintraub J P, Cohen P L
Department of Medicine, University of North Carolina, Chapel Hill 27599-7280, USA.
Clin Immunol. 1999 Jun;91(3):302-9. doi: 10.1006/clim.1999.4717.
Defective Fas-mediated apoptosis in mice, caused by the gld mutation in the fas ligand gene, results in the development of lupus-like autoantibodies and severe lymphoproliferation. We previously demonstrated ectopic expression of the costimulatory molecule B7-1 (CD80) on T lymphocytes in B6/gld mice. This report extends these observations by demonstrating similar results in B6/lpr mice, which possess a mutation in the gene encoding Fas. Additionally, we demonstrate that this phenomenon is age-dependent and occurs on multiple subsets of B6/gld T lymphocytes. B7-1 upregulation is observed on T cells from both conventionally housed and specific-pathogen-free B6/gld mice, suggesting that this is not a consequence of infection by pathogen. T cells from lpr and gld mice show increased binding of CTLA4-Ig fusion protein, suggesting that the upregulated B7-1 is functional. CD28, a receptor for B7-1 which activates T cells, is upregulated in B6/lpr and B6/gld mice, while CTLA4, a negative regulator of T cells which binds B7-1, is not. Our results suggest that ectopic expression of B7-1 on T cells of lpr and gld mice may be playing a role in exacerbation of lymphoproliferation and/or autoimmunity.
Fas配体基因中的gld突变导致小鼠Fas介导的凋亡存在缺陷，进而引发狼疮样自身抗体的产生和严重的淋巴细胞增殖。我们之前证明，在B6/gld小鼠的T淋巴细胞上共刺激分子B7-1（CD80）存在异位表达。本报告通过在编码Fas的基因存在突变的B6/lpr小鼠中得到类似结果，扩展了这些观察结果。此外，我们证明这种现象与年龄有关，并且发生在B6/gld T淋巴细胞的多个亚群上。在常规饲养和无特定病原体的B6/gld小鼠的T细胞上均观察到B7-1上调，这表明这不是病原体感染的结果。来自lpr和gld小鼠的T细胞显示出CTLA4-Ig融合蛋白结合增加，表明上调的B7-1具有功能。B7-1的受体CD28可激活T细胞，在B6/lpr和B6/gld小鼠中上调，而与B7-1结合的T细胞负调节因子CTLA4则没有上调。我们的结果表明，lpr和gld小鼠T细胞上B7-1的异位表达可能在淋巴细胞增殖和/或自身免疫的加重中起作用。
