Host CD4+ CD25+ T cells can expand and comprise a major component of the Treg compartment after experimental HCT
Host CD4+ CD25+ T cells can expand and comprise a major component of the Treg compartment after experimental HCT
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DOI：
10.1182/blood-2008-08-173179
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发表时间：
2009-01-15
期刊：
影响因子：
20.3
通讯作者：
Levy, Robert B.
中科院分区：
文献类型：
--
作者：
Bayer, Allison L.;Jones, Monica;Levy, Robert B.
造血细胞移植（HCT）后受体淋巴室的重建通常是延迟的。本研究调查了几种调理方案后的残留宿主CD4(+) CD25(+) Foxp3(+) （Treg）区，包括T细胞枯竭和T细胞充满的HCT，并观察到(1)少数受体Treg细胞存活于侵袭性调理；(2)残存Tregs显著扩张；(3)受体CD4(+) FoxP3（+）细胞在同基因HCT后的几个月内占Treg区室的大部分。值得注意的是，残余Tregs在T细胞耗尽（TCD）主要组织相容性复合物匹配的异体骨髓hct后也占主导地位，但在T细胞充满移植后却没有。通过体外淋巴抑制和体内自身免疫性疾病转移试验评估，剩余的Treg细胞室功能正常。这些观察结果支持这样一种观点，即功能性宿主treg最初在淋巴细胞减少移植受体中占据一个生态位，经历显著的扩张，并在供体来源的CD4(+)FoxP3(+) T细胞最终构成大部分腔室之前的很长一段时间内为腔室做出贡献。总的来说，研究结果表明，在移植后早期，涉及自体和某些同种异体HCT方案的受者中，宿主Tregs的存在可能是引起免疫反应（如抗肿瘤、疫苗）的重要因素。（Blood. 2009; 113: 733-743）
Reconstitution of the recipient lymphoid compartment following hematopoietic cell transplantation (HCT) is typically delayed. The present studies investigated the residual host CD4(+) CD25(+) Foxp3(+) (Treg) compartment after several conditioning regimens, including T cell depleted and T cell-replete HCT and observed (1) a small number of recipient Treg cells survived aggressive conditioning; (2) the surviving, that is, residual Tregs underwent marked expansion; and (3) recipient CD4(+) FoxP3(+) cells composed the majority of the Treg compartment for several months post-syngeneic HCT. Notably, residual Tregs also dominated the compartment post-HCT with T cell depleted (TCD) major histocompatibility complex-matched allogeneic bone marrow but not following T cell-replete transplantations. The residual Treg cell compartment was functionally competent as assessed by in vitro lymphoid suppression and in vivo autoimmune disease transfer assay. These observations support the notion that functional host Tregs initially occupy a niche in lymphopenic transplantation recipients, undergo significant expansion, and contribute to the compartment for an extended period before donor-derived CD4(+)FoxP3(+) T cells eventually compose the majority of the compartment. In total, the findings suggest that the presence of host Tregs may be important to consider regarding elicitation of immune (eg, antitumor, vaccine) responses in recipients during the early post-transplant period involving autologous and certain allogeneic HCT regimens. (Blood. 2009; 113: 733-743)