Powrie F, Leach M W, Mauze S, Menon S, Caddle L B, Coffman R L
DNAX Research Institute of Molecular and Cellular Biology Incorporated, Palo Alto, California 94040, USA.
Immunity. 1994 Oct;1(7):553-62. doi: 10.1016/1074-7613(94)90045-0.
We have described a murine model of IBD that was induced in C.B-17 scid mice by transfer of the CD45RBhi subpopulation of CD4+ T cells from normal BALB/c mice and could be prevented by cotransfer of the CD45RBlo 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 rIL-10, but not with rIL-4.
我们已经描述了一种炎症性肠病（IBD）的小鼠模型，该模型通过将正常BALB/c小鼠的CD4+ T细胞中CD45RBhi亚群转移至C.B-17 scid小鼠中诱导产生，并且通过共转移CD45RBlo CD4+ T细胞亚群可以预防。在此，我们剖析了该模型中IBD的发病机制，并将此信息用于该疾病的合理免疫治疗。来自患病小鼠的CD4+细胞在体外多克隆刺激后呈现出高度极化的Th1细胞因子合成模式。在T细胞转移后不久给小鼠施用抗IFNγ单克隆抗体可预防结肠炎发展长达12周。用抗TNF单克隆抗体持续中和TNF可降低严重疾病的发生率；然而，仅在最初3 - 4周中和TNF没有效果。用rIL-10全身治疗的小鼠中严重结肠炎完全消除，但用rIL-4治疗则无效。
