CD4^+CD25^+免疫调节性T细胞对CD4^+T细胞介导的移植物抗宿主病预防作用的研究

Prevention of CD4^+T cell-mediated graft-versus-host disease by CD4^+CD25^+T regulatory cells

目的:研究CD4+CD25+免疫调节性T(Treg)细胞在小鼠骨髓移植后,对移植物抗宿主病的预防作用及其作用机制。方法:用C3H(H2k)小鼠骨髓作为供体,提取C3H(H2k)小鼠CD4+T及CD4+CD25+T细胞,C3H×B6(H2k/b)F1小鼠为骨髓移植的受者。在受者接受致死量全身放射后,输注供者去除T细胞的骨髓(ATBM),使其造血功能重建(ATBM组)。于不同的实验组给予CD4+(CD4组)T细胞,CD4+CD25+T(CD25组)或二者同时输注(CD4/CD25组)。观察各组小鼠移植物抗宿主病(GVHD)的发生率。结果:所有10只ATBM组小鼠至骨髓移植后60天仍全部存活,无GVHD发生;所有10只CD4组小鼠在骨髓移植10天内全部死于GVHD(P<0.01);所有5只CD25组小鼠于骨髓移植后60天仍全部存活,无明显GVHD发生(P>0.05);同样,所有6只CD4/CD25组小鼠至骨髓移植后仍全部存活,无明显GVHD发生(P>0.05)。结论:在同种异基因小鼠的骨髓移植模型中,CD4+CD25+T不诱导GVHD的发生,并有预防CD4+T细胞介导的GVHD发生的作用。

Objective：To investigate if CD4^＋ CD25^＋ regrating T cells can suppress GVHD mediated by CD4^＋ T cells in mufine semi-allogeneic bone marrow transplantation model and try to figure out the mechanisms evolved. Methods：C3H （H-2k） as donors, C3H x B6 （H-2k/b） F1 （recipients） were lethally irradiated and reconstituted with antibody T cell depleted bone marrow（ ATBM）, and divided into 4 groups ： （ A ） No further treatment （ n = 10 ） ; （ B ） Infused 5 x 10^5 C3 H CD4^＋ T cells （ CD4, n = 10 ） ; （ C ） Infused 5 × 10^5 CD46＋ CD25^＋ Treg（ CD25, n = 5 ） ; （D） Infused 5 × 105 CD4^＋ T cells plus 5 × 105 CD4^＋ CD25^＋ Treg （ CD4/CD25, n = 6 ）. Results ： All mice in ATBM group, CD25 group and CD4/CD25 groups survived until 60 days without any GVHD symptoms, while all mice in CD4 group died in 10 days from GVHD. Conclusion ： CD4^＋ CD25^＋ Treg cells did not cause GVHD and can prevent GVHD mediated by CD4 ^＋ cells while co-injected with CD4^＋ T cells.