Zhang Baojun, Zhang Aijun, Qu Yanyan, Liu Jun, Niu Zeqing, Zhao Yong
Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Transpl Immunol. 2009 Jan;20(3):180-5. doi: 10.1016/j.trim.2008.09.006. Epub 2008 Oct 7.
Xenogeneic thymus transplantation is an effective strategy to induce tolerance to donors mainly by clonal depletion of reactive T cells. Recent studies have shown that functional mouse CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) could efficiently populate in the periphery of athymic mice after grafting with neonatal pig thymus. However, it is still unknown whether xenogeneic thymus grafts could directly support the development of mouse CD4(+)CD25(+)Foxp3(+) Treg cells as an autogeneic counterpart. Our results show that the percentages of mouse CD4(+)CD8(-)CD25(+) thymocytes are similar among auto- and xenogeneic thymic grafts in thymic mouse recipients. Mouse CD4(+)CD8(-)CD25(+) thymocytes maturing in xenogeneic thymic grafts exhibit similar expressions of Foxp3, TCR, CTLA-4 and GITR as those in autogeneic thymic grafts. Moreover, mouse CD4(+)CD8(-)CD25(+) thymocytes maturing in xenogeneic thymic grafts showed a significant immunosuppressive function on the proliferation of CD4(+)CD25(-) T cells stimulated with Con A or allogeneic antigens, although they showed weaker effects than those maturing in autogeneic thymic grafts. Therefore, the present data provides direct evidence for the ability of xenogeneic porcine thymus grafts to support the development of mouse naturally occurring CD4(+)CD25(+)Foxp3(+) Treg cells.
异种胸腺移植是一种主要通过清除反应性T细胞克隆来诱导对供体产生耐受的有效策略。最近的研究表明，功能性小鼠CD4(+)CD25(+)Foxp3(+)调节性T细胞（Treg）在移植新生猪胸腺后能够有效地在无胸腺小鼠外周组织中聚集。然而，异种胸腺移植是否能像自体胸腺一样直接支持小鼠CD4(+)CD25(+)Foxp3(+) Treg细胞的发育仍不清楚。我们的结果显示，在胸腺小鼠受体中，自体和异种胸腺移植的小鼠CD4(+)CD8(-)CD25(+)胸腺细胞百分比相似。在异种胸腺移植中成熟的小鼠CD4(+)CD8(-)CD25(+)胸腺细胞与在自体胸腺移植中成熟的细胞相比，Foxp3、TCR、CTLA-4和GITR的表达相似。此外，在异种胸腺移植中成熟的小鼠CD4(+)CD8(-)CD25(+)胸腺细胞对用刀豆蛋白A或同种异体抗原刺激的CD4(+)CD25(-) T细胞增殖具有显著的免疫抑制功能，尽管其作用比在自体胸腺移植中成熟的细胞弱。因此，目前的数据为异种猪胸腺移植支持小鼠天然存在的CD4(+)CD25(+)Foxp3(+) Treg细胞发育的能力提供了直接证据。
