CD25+CD4+ regulatory T cells generated by exposure to a model protein antigen prevent allograft rejection:: antigen-specific reactivation in vivo is critical for bystander regulation
CD25+CD4+ regulatory T cells generated by exposure to a model protein antigen prevent allograft rejection:: antigen-specific reactivation in vivo is critical for bystander regulation
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DOI：
10.1182/blood-2004-10-3888
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发表时间：
2005-06-15
期刊：
影响因子：
20.3
通讯作者：
Bushell, AR
中科院分区：
文献类型：
--
作者：
Karim, M;Feng, G;Bushell, AR
CD25(+)CD4(+)调节性T(Treg)细胞在控制免疫反应中的重要性已被确定，但其体内抗原特异性仍不清楚。如果要开发 Treg 细胞用于免疫治疗的潜力，了解 Treg 细胞的特异性要求将非常重要。用供体同种异体抗原和抗 CD4 抗体对受体小鼠进行预处理，产生 CD25(+)CD4(+) Treg 细胞，具有防止过继移植受者皮肤同种异体移植排斥的能力。在这里，我们证明，虽然这种调节可能是抗原特异性的，但用原始耐受同种异体抗原重新激活可以使 Treg 细胞抑制第三方同种异体移植物的排斥。意识到同种异体抗原预处理的局限性，我们询问是否可以针对不相关的非移植抗原产生移植保护性 Treg 细胞。我们证明，旁观者调节也延伸到通过暴露于抗CD4抗体覆盖下的标称抗原体内产生的CD25(+)CD4(+) Treg细胞。如果这些 Treg 细胞在过继转移之前重新暴露于耐受性抗原，它们可以防止完全同种异体皮肤移植的排斥。这可能构成临床相关耐受诱导策略的基础，事实证明，当与亚治疗抗CD8抗体结合时，响应非移植物抗原而产生的Treg细胞促进原代受体接受同种异体心脏移植物。 (c) 2005 年，美国血液学会。
The importance of CD25(+)CD4(+) regulatory T (Treg) cells in the control of immune responses is established, but their antigen specificity in vivo remains unclear. Understanding Treg-cell specificity requirements will be important if their potential is to be developed for immunotherapy. Pretreatment of recipient mice with donor alloantigen plus anti-CD4 antibody generates CD25(+)CD4(+) Treg cells with the capacity to prevent skin allograft rejection in adoptive transfer recipients. Here we demonstrate that, although this regulation can be antigen-specific, reactivation with the original tolerizing alloantigen allows the Treg cells to suppress rejection of third-party allografts. Aware of the limitations of alloantigen pretreatment, we asked whether graft-protective Treg cells could be generated against unrelated, nongraft antigens. We demonstrate that bystander regulation also extends to CD25(+)CD4(+) Treg cells generated in vivo by exposure to nominal antigens under anti-CD4 antibody cover. Providing these Treg cells are reexposed to the tolerizing antigens before adoptive transfer, they prevent the rejection of fully allogeneic skin grafts. That this might form the basis of a clinically relevant tolerance induction strategy is demonstrated by the fact that, when combined with subtherapeutic anti-CD8 antibody, Treg cells generated in response to nongraft antigens facilitate the acceptance of cardiac allografts in primary recipients. (c) 2005 by The American Society of Hematology.