Cutting edge: In vivo trogocytosis as a mechanism of double negative regulatory T cell-mediated antigen-specific suppression
Cutting edge: In vivo trogocytosis as a mechanism of double negative regulatory T cell-mediated antigen-specific suppression
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DOI：
10.4049/jimmunol.181.4.2271
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发表时间：
2008-08-15
影响因子：
4.4
通讯作者：
Zhang, Li
中科院分区：
文献类型：
--
作者：
McIntyre, Megan S. Ford;Young, Kevin J.;Zhang, Li
最近的数据表明，使用 alpha beta-TCR(+)CD3(+)CD4(-)CD8(-)NKI.1(-) 双阴性 (DN) 调节性 T 细胞 (Treg) 治疗可抑制自身免疫性糖尿病，并以 Ag 特异性方式增强同种异体移植和异种移植的存活率。然而，DN Tregs 抑制 Ag 特异性免疫反应的机制仍然很大程度上未知。在这项研究中，我们证明小鼠 DN Tregs 通过胞吞作用在体内获得同种抗原，并将其表达在细胞表面。 Trogocytosis 需要 APC 上的 MHC 肽和 DN Tregs 上的 Ag 特异性 TCR 发生特异性相互作用，因为阻断这种相互作用可以防止 DN Treg 介导的 Trogocytosis。 DN Tregs 需要获得同种异体抗原才能杀死同基因 CD8(+) T 细胞。重要的是，获得同种异体抗原的 DN Tregs 对 Ag 特异性但对 Ag 非特异性同基因 CD8(+) T 细胞没有细胞毒性。这些数据为 Tregs 如何介导 Ag 特异性 T 细胞抑制提供了新的见解，并可能增强我们使用 DN Tregs 治疗移植排斥和自身免疫性疾病的能力。
Recent data have demonstrated that treatment with alpha beta-TCR(+)CD3(+)CD4(-)CD8(-)NKI.1(-) double negative (DN) regulatory T cells (Tregs) inhibits autoimmune diabetes and enhances allotransplant and xenotransplant survival in an Ag-specific fashion. However, the mechanisms whereby DN Tregs suppress Ag-specific immune responses remain largely unknown. In this study, we demonstrate that murine DN Tregs acquire alloantigen in vivo via trogocytosis and express it on their cell surface. Trogocytosis requires specific interaction of MHC-peptide on APCs and Ag-specific TCR on DN Tregs, as blocking this interaction prevents DN Treg-mediated trogocytosis. Acquisition of alloantigen by DN Tregs was required for their ability to kill syngeneic CD8(+) T cells. Importantly, DN Tregs that had acquired alloantigen were cytotoxic toward Ag-specific, but not Ag-nonspecific, syngeneic CD8(+) T cells. These data provide new insight into how Tregs mediate Ag-specific T cell suppression and may enhance our ability to use DN Tregs as a therapy for transplant rejection and autoimmune diseases.