MURINE LUPUS IN MRL/LPR MICE LACKING CD4 OR CD8 T-CELLS
MURINE LUPUS IN MRL/LPR MICE LACKING CD4 OR CD8 T-CELLS
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DOI：
10.1002/eji.1830250923
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发表时间：
1995-09-01
影响因子：
5.4
通讯作者：
MAK, TW
中科院分区：
文献类型：
--
作者：
KOH, DR;HO, A;MAK, TW
MRL/LPR小鼠会形成一种系统性自身免疫性疾病，类似于人类的全身性红斑狼疮。由于CD4（ - ）8（ - ）（dn）B220（+）αβ（+）T细胞的非同寻常群体的积累，小鼠表现出进行性淋巴结病。我们通过基因通过在胚胎干细胞中的同源重组靶向CD4（+）或CD8（+）T细胞的小鼠饲养MRL/LPR小鼠，以确定这些细胞在自身免疫性疾病中的作用。 CD8 - / - IPV和同窝对照组之间的存活率或自身抗体水平没有差异。有趣的是，这些CD8 - / - LPR小鼠的B220（+）DN T细胞水平降低，尽管淋巴结肿大的程度没有改变。 CD4 - / - IPR小鼠的自身免疫性疾病减少，自身抗体产生和皮肤血管降低，与同窝仔对控制相比，生存率增加。然而，由于DNB220（+）T细胞的积累，CD4 - / - EPR小鼠的脾肿性增强了16-20周龄（比IPR对照小鼠大5至8个）。此外，尽管CD4 - / - LPR小鼠的DNB220（+）T细胞的比例高约双重，但外周淋巴结肿大没有差异，但这些细胞与对照IPR小鼠的DN种群在表型上相同。表明积累的DN T细胞可以与这些小鼠的自身免疫性疾病分离，我们的结果表明，自身免疫性疾病取决于CD4（+），但不取决于CD8（+）T细胞，并且许多B220（+）DN T细胞中的许多遍历CD8发育途径。
MRL/lpr mice develop a systemic autoimmune disease similar to systemic lupus erythematosus in humans. The mice show progressive lymphadenopathy due to the accumulation of an unusual population of CD4(-)8(-)(DN) B220(+) alpha beta(+) T cells. We bred MRL/lpr mice with mice lacking CD4(+) or CD8(+) T cells by gene targeting via homologous recombination in embryonal stem cells to determine the roles of these cells in the autoimmune disease. No difference in survival or autoantibody levels was noted between CD8-/- Ipv and littermate controls. Interestingly, these CD8-/- lpr mice have a reduced level of B220(+) DN T cells despite the fact that the degree of lymphadenopathy was unaltered. CD4-/- Ipr mice had a diminished autoimmune disease with a reduction in autoantibody production and skin vasculitits, and increased survival compared to littermate controls. However, CD4-/- Epr mice had an enhanced splenomegaly that developed massively by 16-20 weeks of age (5 to 8 greater than Ipr control mice) due to the accumulation of DNB220(+) T cells. In addition, there were no differences in peripheral lymph node enlargement, although the proportion of DNB220(+) T cells was about twofold higher in the CD4-/- lpr mice, These cells were phenotypically identical to the DN population in control Ipr mice, indicating that the accumulating DN T cells can be dissociated from the autoimmune disease in these mice, Collectively, our results reveal that the autoimmune disease is dependent on CD4(+), but not CD8(+) T cells, and that many of the B220(+)DN T cells traverse a CD8 developmental pathway.