Minor H antigen HA-1-specific regulator and effector CD8+ T cells, and HA-1 microchimerism, in allograft tolerance
Minor H antigen HA-1-specific regulator and effector CD8+ T cells, and HA-1 microchimerism, in allograft tolerance
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DOI：
10.1084/jem.20031012
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发表时间：
2004-04-05
影响因子：
15.3
通讯作者：
Burlingham, WJ
中科院分区：
文献类型：
--
作者：
Cai, JC;Lee, J;Burlingham, WJ
探讨了造血谱系限制性次要组织相容性（H）抗原HA-1在肾移植耐受中的作用。我们从三名组织相容性白细胞抗原（HLA）匹配、HA-1不匹配的肾移植受者中采集外周血样本，其中一名受者在30年前停止免疫抑制，但仍维持正常的肾功能。将外周血单个核细胞（PBMC）注射到严重联合免疫缺陷小鼠的足垫中以测量人迟发型超敏反应（DTH）。所有三名患者均表现出对HA-1（H）肽的调节DTH反应。通过不同的四聚体染色强度，我们观察到两个不同的次要H抗原HA-1特异性CD 8（+）T细胞亚群。染色模糊的细胞具有T调节（T-R）细胞的特征，并产生白细胞介素（IL）10和/或转化生长因子（TGF）β。这些HA-1特异性T-R细胞与枯萎病四聚体结合的CD 8（+）T效应（T-E）细胞共存。CD 8（+）T-E细胞介导HA-1特异性DTH并产生干扰素-γ。T-R细胞对这些T1功能的抑制依赖于TGF β、IL-10和细胞毒性T淋巴细胞相关抗原4。此外，HA-1微嵌合体检测在两个收件人，主要是在树突状细胞部分的PBMC。这是首次证实在肾移植耐受的背景下，CD 8（+）记忆T-R和T-E细胞共存，两者对相同的HA-1抗原具有特异性。
The role of the hematopoietic lineage-restricted minor histocompatibility (H) antigen HA-1 in renal allograft tolerance was explored. We obtained peripheral blood samples from three recipients of histocompatibility leukocyte antigen (HLA)-matched, HA-1-mismatched renal transplants, one of which had discontinued immunosuppression >30 yr ago while sustaining normal kidney function. Peripheral blood mononuclear cells (PBMCs) were injected into the footpads of severe combined immunodeficiency mice to measure human delayed type hypersensitivity (DTH) responses. All three patients manifested regulated DTH responses to HA-1(H) peptide. By differential tetramer staining intensities, we observed two distinct minor H antigen HA-1-specific CD8(+) T cell subsets. The one that stained dimly had the characteristics of a T regulatory (T-R) cell and produced interleukin (IL)10 and/or transforming growth factor (TGF) beta. These HA-1-specific T-R cells coexisted with blight tetramer-binding CD8(+) T effector (T-E) cells. The CD8(+) T-E cells mediated HA-1-specific DTH and produced interferon-gamma. Suppression of these T, functions by T-R cells was TGFbeta, IL-10, and cytotoxic T lymphocyte-associated antigen 4 dependent. In addition, HA-1 microchimerism was detected in two recipients, primarily in the dendritic cell fraction of the PBMCs. This is the first demonstration of coexisting CD8(+) memory T-R, and T-E cells, both specific for the same HA-1 antigen, in the context of renal allograft tolerance.