Circulating activated and effector memory T cells are associated with calcification and clonal expansions in bicuspid and tricuspid valves of calcific aortic stenosis.
Circulating activated and effector memory T cells are associated with calcification and clonal expansions in bicuspid and tricuspid valves of calcific aortic stenosis.
复制标题
DOI：
10.4049/jimmunol.1003521
复制
发表时间：
2011-07-15
期刊：
影响因子：
--
通讯作者：
Stewart AS
中科院分区：
文献类型：
--
作者：
Winchester R;Wiesendanger M;O'Brien W;Zhang HZ;Maurer MS;Gillam LD;Schwartz A;Marboe C;Stewart AS
我们试图进一步描述钙化性主动脉瓣狭窄（CAS）中浸润瓣叶的T淋巴细胞的免疫学意义，并确定循环T细胞是否存在相关改变。使用克隆型TCR β链长度和序列分析，我们证实了三尖瓣CAS瓣膜的所有组成部分包含大量扩增的T细胞克隆，具有不同程度的额外多克隆性，这在严重钙化的病例中最大。我们现在报告了在更年轻的二尖瓣CAS病例中克隆性扩张的相似比例。外周血流式细胞术显示HLA-DR+活化的CD 8细胞和CD 8 + CD 28 nullCD 57+记忆效应子亚群的升高，在瓣膜钙化更严重的二尖瓣和三尖瓣CAS病例中显著更大。CD 4 + CD 28 null T细胞的增加较少，主要是在并发动脉粥样硬化疾病的病例中。免疫染色显示，所有瓣膜中的CD 8 T细胞主要为CD 28 null，寡克隆瓣膜中的CD 8 T细胞百分比最高。通过其克隆型序列识别的T细胞克隆在瓣膜中扩增，也发现在循环血液CD 28 nullCD 8 + T细胞中扩增，在CD 8 + CD 28+亚群中扩增程度较低，直接支持血液和瓣膜中免疫事件之间的关系。结果表明，在患有二尖瓣和三尖瓣CAS的病例中正在发生持续的全身适应性免疫应答，涉及循环CD 8 T细胞活化、克隆扩增和分化为记忆效应表型，以及T细胞在血液和瓣膜之间的扩增克隆中的运输。
We sought to delineate further the immunological significance of T lymphocytes infiltrating the valve leaflets in calcific aortic stenosis (CAS) and determine whether there were associated alterations in circulating T cells. Using clonotypic TCR β-chain length and sequence analysis we confirmed the repertoire of tricuspid CAS valves contains numerous expanded T cell clones with varying degrees of additional polyclonality, which was greatest in cases with severe calcification. We now report a similar proportion of clonal expansions in the much younger bicuspid valve CAS cases. Peripheral blood flow cytometry revealed elevations in HLA-DR+ activated CD8 cells and in the CD8+CD28nullCD57+ memory-effector subset that were significantly greater in both bicuspid and tricuspid CAS cases with more severe valve calcification. Lesser increases of CD4+CD28null T cells were identified, principally in cases with concurrent atherosclerotic disease. Upon immunostaining the CD8 T cells in all valves were mainly CD28null, and CD8 T cell percentages were greatest in valves with oligoclonal repertoires. T cell clones identified by their clonotypic sequence as expanded in the valve were also found expanded in the circulating blood CD28nullCD8+ T cells and to a lesser degree in the CD8+CD28+ subset, directly supporting the relationship between immunologic events in the blood and the valve. The results suggest that an ongoing systemic adaptive immune response is occurring in cases with bicuspid and tricuspid CAS, involving circulating CD8 T cell activation, clonal expansion and differentiation to a memory-effector phenotype, with trafficking of T cells in expanded clones between blood and the valve.
登录
查看更多内容
影响因子：
5.3
作者：
Hsu, HC;Scott, DK;Mountz, JD
通讯作者：
Mountz, JD
影响因子：
3.3
作者：
Soini, Y;Salo, T;Satta, J
通讯作者：
Satta, J
影响因子：
82.9
作者：
Gorochov, G;Neumann, AU;Debré, P
通讯作者：
Debré, P
影响因子：
20.3
作者：
Brenchley, JM;Karandikar, NJ;Koup, RA
通讯作者：
Koup, RA
影响因子：
4.4
作者：
Curran, SA;FitzGerald, OM;Winchester, R
通讯作者：
Winchester, R