Alloantigen-specific de novo-induced Foxp3+ Treg revert in vivo and do not protect from experimental GVHD
Alloantigen-specific de novo-induced Foxp3+ Treg revert in vivo and do not protect from experimental GVHD
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DOI：
10.1002/eji.200939432
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发表时间：
2009-11-01
影响因子：
5.4
通讯作者：
Prinz, Immo
中科院分区：
文献类型：
--
作者：
Koenecke, Christian;Czeloth, Niklas;Prinz, Immo
诱导的抗原特异性Foxp 3（+）T细胞（iTreg）正在被讨论为多克隆天然Foxp 3（+）T细胞（nTreg）的有希望的替代物，用于基于细胞的治疗，特别是实现移植耐受。使用Foxp 3eGFP报告小鼠，我们在此建立了一种有效的方案，从Foxp 3（-）CD 4（+）T细胞与簇破坏的DC中诱导和扩增同种异体抗原特异性iTreg。这些iTreg主要为CD 62 L（+），在体外表现出有效的抑制活性。然而，与nTreg相反，过继转移的iTreg完全不能预防致命的移植物抗宿主病（GVHD）。在辐射受体中，大多数过继转移的Foxp 3（+）iTreg，而不是Foxp 3（+）nTreg迅速恢复为Foxp 3（-）CD 4（+）T细胞。因此，我们建议治疗GVHD的治疗方法应依赖于nTreg，而使用从头同种异体抗原诱导的iTreg应谨慎处理，因为iTreg的调节表型的稳定性可能是主要问题。
Induced antigen-specific Foxp3(+) T cells (iTreg) are being discussed as a promising alternative to polyclonal natural Foxp3(+) T cells (nTreg) for cell-based therapies, particularly to achieve transplantation tolerance. Using Foxp3eGFP-reporter mice, we here establish an efficient protocol to induce and expand alloantigen-specific iTreg from Foxp3(-)CD4(+) T cells with cluster-disrupted DC. These iTreg were mainly CD62L(+) and showed efficient suppressive activity in vitro. However, in contrast to nTreg, adoptively transferred iTreg entirely failed to prevent lethal graft versus host disease (GVHD). Within irradiated recipients, the majority of adoptively transferred Foxp3(+) iTreg, but not Foxp3(+) nTreg quickly reverted to Foxp3(-)CD4(+) T cells. We therefore suggest that therapeutic approaches to treat GVHD should rely on nTreg, whereas the use of de novo alloantigen-induced iTreg should be handled with caution since the stability of the regulatory phenotype of the iTreg could be of major concern.