The lymphocytic infiltration in calcific aortic stenosis predominantly consists of clonally expanded T cells

Henry D. Wu, Mathew S. Maurer, Richard A. Friedman, Charles C. Marboe, Elena M. Ruiz-Vazquez, Rajasekhar Ramakrishnan, Allan Schwartz, M. David Tilson, Allan S. Stewart, Robert Winchester

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Valve lesions in degenerative calcific aortic stenosis (CAS), a disorder affecting 3% of those older than 75 years, are infiltrated by T lymphocytes. We sought to determine whether the αβ 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 β-chain CDR3-length distribution analysis using PCR primers specific for 23 Vβ families performed in eight individuals with CAS affecting tri- or bileaflet aortic valves revealed considerable oligoclonal T cell expansion. In five cases, β-chain nucleotide sequencing in five selected Vβ 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 × 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 β-chain CDR3 regions were homologous to TCR β-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 αβ T cells are implicated in mediating a component of the valvular injury responsible for CAS.

Original languageEnglish
Pages (from-to)5329-5339
Number of pages11
JournalJournal of Immunology
Volume178
Issue number8
DOIs
StatePublished - 15 Apr 2007
Externally publishedYes

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