期刊
JOURNAL OF IMMUNOLOGY
卷 178, 期 8, 页码 5329-5339出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.8.5329
关键词
-
类别
资金
- NCRR NIH HHS [M01RR00645] Funding Source: Medline
- NHLBI NIH HHS [R01 HL084599, R01 HL084599-01, R01 HL084599-04] Funding Source: Medline
- NIAID NIH HHS [U19 AI046132] Funding Source: Medline
- NIA NIH HHS [K23-AG00966-A1A] Funding Source: Medline
Valve lesions in degenerative calcitic aortic stenosis (CAS), a disorder affecting 3% of those older than 75 years, are infiltrated by T lymphocytes. We sought to determine whether the alpha beta TCR repertoire of these valve-infiltrating lymphocytes exhibited features either of a polyclonal nonselective response to inflammation or contained expanded clones suggesting a more specific immune process. TCR beta-chain CDR3-length distribution analysis using PCR primers specific for 23 V beta families performed in eight individuals with CAS affecting tri- or bileaflet aortic valves revealed considerable oligoclonal T cell expansion. In five cases, beta-chain nucleotide sequencing in five selected V beta families showed that an average of 92% of the valve-infiltrating T cell repertoire consisted of expanded T cell clones, differing markedly in composition from the relatively more polyclonal peripheral CD8 or CD4 T cell subsets found even in this elderly population. Twenty-four of the valve-infiltrating T cell clones also had the same clone identified in blood, some of which were highly expanded. Interestingly, 22 of these 24 shared clones were CD8 in lineage (p = 1.5 X 10(-12)), suggesting a possible relationship to the expanded CD8(+)CD28(-) T cell clones frequently present in the elderly. Additionally, the sequences of several TCR beta-chain CDR3 regions were homologous to TCR beta-chains identified previously in allograft arteriosclerosis. We infer that these findings are inconsistent with a nonselective secondary response of T cells to inflammation and instead suggest that clonally expanded alpha beta T cells are implicated in mediating a component of the valvular injury responsible for CAS.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据