首页> 外文期刊>Cellular immunology >Suppression of murine experimental autoimmune encephalomyelitis by interleukin-2 receptor targeted fusion toxin, DAB(389)IL-2.
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Suppression of murine experimental autoimmune encephalomyelitis by interleukin-2 receptor targeted fusion toxin, DAB(389)IL-2.

机译:白介素2受体靶向融合毒素DAB(389)IL-2抑制小鼠实验性自身免疫性脑脊髓炎。

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摘要

Previously we have shown that DAB(389)IL-2, a recombinant fusion toxin targeting IL-2R bearing cells, suppressed disease in the rat experimental autoimmune encephalomyelitis (EAE) model of acute multiple sclerosis (MS). Our present study demonstrates that DAB(389)IL-2 can also effectively suppress acute (A)-EAE, relapsing (R)-EAE and chronic (C)-EAE in mouse demyelinating models. DAB(389)IL-2 significantly suppressed mitogenic proliferation of spleen cells while mutant fusion proteins DA(glu53)B(389)IL-2 and DAB(389)IL-2(8-10) did not. EAE was successfully suppressed when DAB(389)IL-2 was administered in various regimens between days 1 and 15 post immunization in all three models. CD4(+)IL-2R(+) cells were reduced in the spleen but not in the lymph nodes of DAB(389)IL-2-treated mice during A-EAE while the number of CD8(+) cells was unchanged. DAB(389)IL-2 also significantly reduced the number of CD4(+), CD8(+), CD25(+), TCRgammadelta(+) phenotype and CD11b(+) macrophages/microglia within spinal cord lesions. These data strongly suggest that DAB(389)IL-2 specifically targeted myelin protein-activated CD4(+) T cells and strengthens the argument for the use of DAB(389)IL-2 in treatment strategies for MS.
机译:以前我们已经证明DAB(389)IL-2是一种针对IL-2R携带细胞的重组融合毒素,可在大鼠实验性自身免疫性脑脊髓炎(EAE)急性多发性硬化症(MS)模型中抑制疾病。我们目前的研究表明,DAB(389)IL-2还可以在小鼠脱髓鞘模型中有效抑制急性(A)-EAE,复发性(R)-EAE和慢性(C)-EAE。 DAB(389)IL-2显着抑制了脾细胞的有丝分裂增殖,而突变融合蛋白DA(glu53)B(389)IL-2和DAB(389)IL-2(8-10)却没有。在所有三种模型中,在免疫后第1天至第15天之间以各种方案给予DAB(389)IL-2,均可成功抑制EAE。在A-EAE期间,DAB(389)IL-2处理的小鼠的脾脏中CD4(+)IL-2R(+)细胞减少,而淋巴结中并未减少,而CD8(+)细胞的数量则保持不变。 DAB(389)IL-2还显着减少了脊髓损伤内CD4(+),CD8(+),CD25(+),TCRγδ(+)表型和CD11b(+)巨噬细胞/小胶质细胞的数量。这些数据强烈表明DAB(389)IL-2专门针对髓磷脂蛋白激活的CD4(+)T细胞,并加强了在MS的治疗策略中使用DAB(389)IL-2的观点。

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