Isolation and characterization of human antigen-specific TCRαβ+ CD4-CD8- double-negative regulatory T cells
Isolation and characterization of human antigen-specific TCRαβ+ CD4-CD8- double-negative regulatory T cells
复制标题
DOI：
10.1182/blood-2004-07-2583
复制
发表时间：
2005-04-01
期刊：
影响因子：
20.3
通讯作者：
Mackensen, A
中科院分区：
文献类型：
--
作者：
Fischer, K;Voelkl, S;Mackensen, A
调节性T（Treg）细胞对免疫应答的下调是参与诱导对同种异体抗原（Ags）耐受的重要机制。最近，发现一种新的Ag特异性T细胞受体（TCR）α β（+）CD 4（-）CD 8（-）（双阴性[DN]）Treg细胞亚群能够通过特异性抑制抗移植物特异性CD 8（+）T细胞的功能来预防皮肤和心脏同种异体移植物的排斥反应。在这里，我们证明了外周DN Treg细胞存在于人体中，它们占总CD 3（+）T细胞的约1%，并且由幼稚细胞和Ag经历的细胞组成。与鼠DN Treg细胞类似，人DN Treg细胞能够通过细胞接触依赖性机制从抗原呈递细胞获得肽-HLA-A2复合物。此外，这种获得的肽-HLA复合物似乎具有功能活性，因为对HLA-A2限制性自身肽Melan-A特异的CD 8（+）T细胞在获得Melan-A-HLA-A2复合物后变得对邻近DN T细胞的凋亡敏感，并显示出降低的增殖反应。这些结果第一次证明了在人类中存在能够抑制Ag特异性T细胞的相当大的外周DN Treg细胞群体。DN Treg细胞可用于限制移植后同种抗原特异性T细胞的克隆扩增。
Down-regulation of immune responses by regulatory T (Treg) cells is an important mechanism involved in the induction of tolerance to allo-antigens (Ags). Recently, a novel subset of Ag-specific T-cell receptor (TCR)alpha beta(+) CD4(-)CD8(-)(double-negative [DN]) Treg cells has been found to be able to prevent the rejection of skin and heart allografts by specifically inhibiting the function of antigraft-specific CD8(+) T cells. Here we demonstrate that peripheral DN Treg cells are present in humans, where they constitute about 1% of total CD3(+) T cells, and consist of both naive and Ag-experienced cells. Similar to murine DN Treg cells, human DN Treg cells are able to acquire peptide-HLA-A2 complexes from antigen-presenting cells by cell contact-dependent mechanisms. Furthermore, such acquired peptide-HLA complexes appear to be functionally active, in that CD8(+) T cells specific for the HLA-A2-restricted self-peptide, Melan-A, became sensitive to apoptosis by neighboring DN T cells after acquisition of Melan-A-HLA-A2 complexes and revealed a reduced proliferative response. These results demonstrate for the first time that a sizable population of peripheral DN Treg cells, which are able to suppress Ag-specific T cells, exists in humans. DN Treg cells may serve to limit clonal expansion of allo-Ag-specific T cells after transplantation.