T cells in cardiac allograft vasculopathy are skewed to memory Th-1 cells in the presence of a distinct Th-2 population
T cells in cardiac allograft vasculopathy are skewed to memory Th-1 cells in the presence of a distinct Th-2 population
复制标题
DOI：
10.1111/j.1600-6143.2008.02198.x
复制
发表时间：
2008-05-01
影响因子：
8.8
通讯作者：
de Weger, R. A.
中科院分区：
文献类型：
--
作者：
Hagemeijer, M. C.;van Oosterhout, M. F. M.;de Weger, R. A.
心脏移植（HTx）患者的心脏移植物血管病（CAV）仍然是长期生存的主要并发症，这是由于浸润的单核细胞（MNC）诱导的向心性新生内膜增生。以前，我们发现，激活的记忆性辅助性T细胞-1（Th-1）细胞是CAV冠状动脉浸润MNC的主要成分。在这项研究中，通过研究MNC标记物，对患有CAV的人冠状动脉（n = 5）中的MNC进行了更详细的表征，并与没有CAV的冠状动脉（n = 5）进行了比较（CD 1a、DRC-1、CD 3、CD 20、CD 27、CD 28、CD 56、CD 68、CD 69、FOXP 3和HLA-DR）、细胞因子（IL-1A、2、4、10、12 B、IFN-γ和TGF-β 1）和趋化因子受体（CCR 3，CCR 4，CCR 5，CCR 7，CCR 8，CXCR 3和CX 3CR 1）的免疫组织化学双标记和定量PCR的mRNA分离的激光显微切割冠状动脉层。CAV的新生内膜和外膜中的T细胞倾向于活化的记忆Th-1表型，但存在不同的Th-2群体。未检测到FOXP 3阳性T细胞，除IFN-γ和TGF-β外，大多数细胞因子的产生较低或不存在。辅助性T细胞的这种典型组成，特别是IFN-γ和TGF-β的产生，可能在增殖性CAV反应中起重要作用。
Cardiac allograft vasculopathy (CAV) in heart transplantation (HTx) patients remains the major complication for long-term survival, due to concentric neointima hyperplasia induced by infiltrating mononuclear cells (MNC). Previously, we showed that activated memory T-helper-1 (Th-1) cells are the major component of infiltrating MNC in coronary arteries with CAV. In this study, a more detailed characterization of the MNC in human coronary arteries with CAV (n = 5) was performed and compared to coronary arteries without CAV (n = 5), by investigating MNC markers (CD1a, DRC-1, CD3, CD20, CD27, CD28, CD56, CD68, CD69, FOXP3 and HLA-DR), cytokines (IL-1A, 2, 4, 10, 12B, IFN-gamma, and TGF-beta 1), and chemokine receptors (CCR3, CCR4, CCR5, CCR7, CCR8, CXCR3 and CX3CR1) by immunohistochemical double-labeling and quantitative PCR on mRNA isolated from laser microdissected layers of coronary arteries. T cells in the neointima and adventitia of CAV were skewed toward an activated memory Th-1 phenotype, but in the presence of a distinct Th-2 population. FOXP3 positive T cells were not detected and production of most cytokines was low or absent, except for IFN-gamma, and TGF-beta. This typical composition of T-helper cells and especially production of IFN-gamma and TGF-beta may play an important role in the proliferative CAV reaction.