INHIBITION OF TH1 RESPONSES PREVENTS INFLAMMATORY BOWEL-DISEASE IN SCID MICE RECONSTITUTED WITH CD45RB(HI) CD4(+) T-CELLS
INHIBITION OF TH1 RESPONSES PREVENTS INFLAMMATORY BOWEL-DISEASE IN SCID MICE RECONSTITUTED WITH CD45RB(HI) CD4(+) T-CELLS
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DOI：
10.1016/1074-7613(94)90045-0
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发表时间：
1994-10-01
期刊：
影响因子：
32.4
通讯作者：
COFFMAN, RL
中科院分区：
文献类型：
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作者：
POWRIE, F;LEACH, MW;COFFMAN, RL
我们描述了一种 IBD 小鼠模型，该模型是通过从正常 BALB/c 小鼠转移 CD4(+) T 细胞的 CD45RB(hi) 亚群在 C.B-17 scid 小鼠中诱导的，并且可以通过共转移 CD45RB(lo) CD4(+) T 细胞亚群来预防。在这里，我们剖析了该模型中IBD的发病机制，并利用这些信息对该疾病进行合理的免疫治疗。来自患病小鼠的CD4(+)细胞在体外多克隆刺激后表现出高度极化的Th1细胞因子合成模式。 T 细胞移植后不久，对小鼠施用抗 IFN γ MAb 可在长达 12 周的时间内阻止结肠炎的发展。用抗 TNF MAb 持续中和 TNF 可降低严重疾病的发生率；然而，仅在前 3-4 周内中和 TNF 就没有效果。在用 rIL-10 全身治疗的小鼠中，严重结肠炎被完全消除，但用 rIL-4 则没有。
We have described a murine model of IBD that was induced in C.B-17 scid mice by transfer of the CD45RB(hi) subpopulation of CD4(+) T cells from normal BALB/c mice and could be prevented by cotransfer of the CD45RB(lo) CD4(+) T cell subset. Here we have dissected the mechanism of pathogenesis of IBD in this model and used this information for rational immunotherapy of the disease. CD4(+) cells from diseased mice displayed a highly polarized Th1 pattern of cytokine synthesis upon polyclonal stimulation in vitro. The administration of anti-IFN gamma MAb to mice soon after T cell transfer prevented development of colitis for up to 12 weeks. Continual neutralization of TNF with anti-TNF MAbs reduced the incidence of severe disease; however, neutralization of TNF during only the first 3-4 weeks had no effect. Severe colitis was completely abrogated in mice treated systemically with rlL-10, but not with rlL-4.