Lakkis F G, Konieczny B T, Saleem S, Baddoura F K, Linsley P S, Alexander D Z, Lowry R P, Pearson T C, Larsen C P
Department of Medicine (Renal Division), Emory University School of Medicine, Atlanta, GA 30033, USA.
J Immunol. 1997 Mar 1;158(5):2443-8.
Blocking the CD28-B7 T lymphocyte costimulatory pathway with the recombinant protein CTLA4Ig induces long term allograft survival in rodents. It has been suggested that this results from selective activation of the Th2 immune pathway. To test this hypothesis, we compared vascularized cardiac allograft survival in wild-type (IL-4 +/+) and homozygous IL-4 gene-knockout (IL-4 -/-) mice. We report in this study that long term survival (>100 days) of fully allogeneic grafts can be induced readily in IL-4 -/- recipients treated with a short course of CTLA4Ig. We also demonstrate that IL-4 -/- mice are deficient in Th2-type cytokine expression following in vitro or in vivo allostimulation. These results suggest that IL-4 production and subsequent generation of a Th2-type immune response are not obligatory for CTLA4Ig-induced long term acceptance of vascularized allografts.
用重组蛋白CTLA4Ig阻断CD28 - B7 T淋巴细胞共刺激途径可诱导啮齿动物同种异体移植物长期存活。有人认为，这是Th2免疫途径选择性激活的结果。为了验证这一假设，我们比较了野生型（IL - 4 +/+）和纯合IL - 4基因敲除（IL - 4 -/-）小鼠中血管化心脏同种异体移植物的存活情况。我们在本研究中报告，在用短疗程CTLA4Ig治疗的IL - 4 -/-受体中，完全同种异体移植物的长期存活（>100天）很容易被诱导。我们还证明，IL - 4 -/-小鼠在体外或体内异体刺激后Th2型细胞因子表达存在缺陷。这些结果表明，IL - 4的产生以及随后Th2型免疫反应的产生对于CTLA4Ig诱导的血管化同种异体移植物的长期接受不是必需的。
