Role of inducible costimulator (ICOS) in the development of an autoimmune disease

1. Icos缺陷型MRL/lpr小鼠的产生Icos缺陷型小鼠与MRL/lpr小鼠回交7代。将Icos +/-小鼠进行杂交，产生icos+/+ MRL/lpr和icos-/- MRL/lpr小鼠。2.脾细胞增殖和脾肿大icos-/-MRL/lpr小鼠的淋巴结肿大程度较icos+/+ MRL/lpr小鼠轻，但脾肿大程度与icos+/+ MRL/lpr小鼠相似。MRL/lpr小鼠B220-T细胞和CD 4 + T细胞较对照组减少。关于脾CD 4 + T细胞，在icos-/- MRL/lpr小鼠中注意到记忆T细胞和B22 O-CD 4 + T细胞的减少。CD 4 + T细胞胞内细胞因子染色显示，icos-/- MRL/ipr小鼠IFN-γ阳性细胞/IL-4阳性细胞比例降低。结果表明，icos-/- MRL/lpr小鼠的CD 4 + T细胞中，与icos+/+ MRL/lpr小鼠相比，细胞因子平衡偏向于Th 2。4.自身抗体：与icos +/+ MRL/lpr小鼠相比，icos-/- MRL/lpr小鼠血清中IgG 1、IgG 2a和IgM亚类的抗dsDNA抗体水平降低，但IgG 3亚类的水平没有降低。6.肾小球肾炎icos-/-MRL/lpr小鼠与icos +/+ MRL/lpr小鼠肾小球肾炎的严重程度无明显差异。然而，在icos-/- MRL/lpr小鼠中，血管周围和间质的炎性细胞浸润被完全消除。

1.Generation of icos-deficient MRL/lpr miceIcos-deficient mice were backcrossed into MRL/lpr mice for seven generations. Icos +/- mice were intercrossed, and icos+/+ MRL/lpr and icos-/- MRL/lpr mice were generated.2.Lymphoproliferation and splenomegalyIcos-/-MRL/lpr mice showed less severe lymphadenopathy, but similar level of splenomegaly as compared with those in icos+/+ MRL/lpr mice.3.Analysis of spleen cellsIn the spleen from iocs-/- MRL/lpr mice, B220-T cells and CD4+ T cells were reduced as compared with that from control MRL/lpr mice. Regarding splenic CD4+ T cells, the reduction of memory T cells and B22O-CD4+ T cells were noted in icos-/- MRL/lpr mice. The intracellular cytokine staining of CD4+ T cells showed that the ratio of IFN-gamma-positive calls/IL-4-positive cell was decreased in icos-/- MRL/ipr mice. The result indicates that in CD4+ T cells from icos-/- MRL/lpr mice, cytokine balance is biased to Th2 as compared with that in icos+/+ MRLlpr mice4.AutoantibodiesIn icos-/- MRL/lpr mice, serum anti-dsDNA antibody levels of IgG1,IgG2a,and IgM subclasses, but not IgG3 subclass were decreased as compared with those in icos+/+ MRL/lpr mice.5.Cytokine levelsIn icos-/- MRL/lpr mice, serum levels of MCP-1 and IL-12p70 were lower than those in icos+/+ MRL/lpr mice.6.GlomerulonephritisThe severity of glomerulonephritis was not different between icos-/- MRL/lpr mice and icos+/+ MRL/lpr mice. However, perivascular and interstitial infiltration of inflammatory cells was completely abolished in icos-/- MRL/lpr mice.