Department of Pathology, Faculty of Medicine, University of Manitoba, 401 Brodie Center, 727 McDermot Avenue, Winnipeg, MB, Canada.
J Clin Immunol. 2011 Jun;31(3):406-13. doi: 10.1007/s10875-010-9491-5. Epub 2010 Dec 15.
Using the C57BL/6→(C57BL/6 x DBA/2)F(1)-hybrid model of acute graft-versus-host disease (GVHD), we previously showed that treating the donor mice with palifermin provides protection from morbidity and a shift from Th1 to Th2 cytokine production. To determine whether thymic stromal lymphopoietin (TSLP) is involved in palifermin-mediated immune modulation, we used donors from the following groups: (1) untreated wild-type donors, (2) palifermin-treated wild-type donors, (3) untreated TSLPR(-/-) donors, and (4) palifermin-treated TSLPR(-/-) donors. Survival in the recipients was 0%, 100%, 31%, and 0%, for groups 1-4, respectively, indicating that TSLP responsiveness is required for palifermin-mediated protection from GVHD. We also found that the increases in Th2 cytokine levels that are induced by palifermin treatment are obviated in TSLPR(-/-) donors, and that protection from GVHD (group 2) is associated with a higher percentage of CD4(+)CD25(+)Foxp3(+) cells in the graft. Collectively, our findings show that when palifermin and TSLP act in concert, the predominant effect is protection in this model.
我们曾利用 C57BL/6→(C57BL/6 x DBA/2)F(1)-急性移植物抗宿主病（GVHD）杂交模型，证实了用培非格司亭治疗供者可预防发病并使 Th1 向 Th2 细胞因子产生转移。为了确定胸腺基质淋巴细胞生成素（TSLP）是否参与培非格司亭介导的免疫调节，我们使用了以下供者组：（1）未经处理的野生型供者，（2）用培非格司亭处理的野生型供者，（3）未经处理的 TSLPR(-/-)供者，和（4）用培非格司亭处理的 TSLPR(-/-)供者。接受者的存活率分别为 0%、100%、31%和 0%，说明 TSLP 反应性是培非格司亭介导的 GVHD 保护所必需的。我们还发现，培非格司亭治疗诱导的 Th2 细胞因子水平升高在 TSLPR(-/-)供者中被消除，而 GVHD 的保护（第 2 组）与移植物中更高比例的 CD4(+)CD25(+)Foxp3(+)细胞有关。总之，我们的研究结果表明，当培非格司亭和 TSLP 协同作用时，该模型中的主要作用是保护。
