前沿：阻断CD28/B7共刺激通路可抑制由CD4+而非CD8+T细胞介导的肠道同种异体移植排斥反应。

Cutting edge: blockade of the CD28/B7 costimulatory pathway inhibits intestinal allograft rejection mediated by CD4+ but not CD8+ T cells.

作者信息

Newell K A, He G, Guo Z, Kim O, Szot G L, Rulifson I, Zhou P, Hart J, Thistlethwaite J R, Bluestone J A

机构信息

Department of Surgery, Committee on Immunology, Ben May Institute for Cancer Research, University of Chicago, IL 60637, USA.

出版信息

J Immunol. 1999 Sep 1;163(5):2358-62.

PMID:10452966

Abstract

The effect of blocking the CD28/B7 costimulatory pathway on intestinal allograft rejection was examined in mice. Murine CTLA4Ig failed to prevent the rejection of allografts transplanted into wild-type or CD4 knockout (KO) mice but did inhibit allograft rejection by CD8 KO recipients. This effect was associated with decreased intragraft mRNA for IFN-gamma and TNF-alpha and increased mRNA for IL-4 and IL-5. This altered pattern of cytokine production was not observed in allografts from murine CTLA4Ig-treated CD4 KO mice. These data demonstrate that blockade of the CD28/B7 pathway has different effects on intestinal allograft rejection mediated by CD4+ and CD8+ T cells and suggest that these T cell subsets have different costimulatory requirements in vivo. The results also suggest that the inhibition of CD4+ T cell-mediated allograft rejection by CTLA4Ig may be related to down-regulation of Th1 cytokines and/or up-regulation of Th2 cytokines.

摘要

在小鼠中研究了阻断CD28/B7共刺激途径对肠道同种异体移植排斥反应的影响。鼠CTLA4Ig未能预防移植到野生型或CD4基因敲除（KO）小鼠体内的同种异体移植排斥反应，但确实抑制了CD8 KO受体的同种异体移植排斥反应。这种作用与移植组织内IFN-γ和TNF-α的mRNA减少以及IL-4和IL-5的mRNA增加有关。在经鼠CTLA4Ig处理的CD4 KO小鼠的同种异体移植中未观察到这种细胞因子产生模式的改变。这些数据表明，阻断CD28/B7途径对由CD4+和CD8+ T细胞介导的肠道同种异体移植排斥反应有不同影响，并表明这些T细胞亚群在体内有不同的共刺激需求。结果还表明，CTLA4Ig对CD4+ T细胞介导的同种异体移植排斥反应的抑制作用可能与Th1细胞因子的下调和/或Th2细胞因子的上调有关。