Predominance of type 1 CD4+ T cells in human abdominal aortic aneurysm

Clin Exp Immunol. 2005 Dec;142(3):519-27. doi: 10.1111/j.1365-2249.2005.02938.x.

Abstract

The functional repertoire of T cells in abdominal aortic aneurysm (AAA) and the exact nature of aortic wall adaptive cellular immune responses still remains a matter of debate. In this study, we sought to determine whether type 1 or type 2 responses occur predominantly in human aneurysmal aortic lesions. We first examined the phenotype and cytokine secretion profile of T lymphocytes freshly isolated from aneurysmal aortic wall for comparison with their circulating counterparts using flow cytometry. We found that both populations of infiltrating CD4(+) and CD8(+)T cells displayed a unique activated memory phenotype. In addition, we identified the presence in human aneurysmal aortic lesion of CD4(+)T cells producing high levels of interferon (IFN)-gamma but not interleukin (IL)-4, reflecting their type 1 nature. Quantitative analysis of cytokine gene expression confirmed increased IFN-gamma transcript levels in infiltrating cells compared to controls. We next analysed aortic wall responses using LightCycler-based quantitative real-time reverse transcription-polymerase chain reaction. Compared to control non-diseased aortic samples, we demonstrated that whole AAA tissues exhibited high mRNA levels of IFN-gamma but not IL-4. Overexpression of the transcription factor T-bet in the absence of significant GATA-3 expression further assessed the type 1 polarization of aortic wall immune responses. These findings indicate that type 1 CD4(+)T cells predominate in human AAA lesions. This study has important implications for the pathogenesis of aneurysm disease. Through the production of IFN-gamma, T cells may indeed contribute to orchestrate extracellular matrix remodelling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD / immunology
  • Aorta, Abdominal / immunology
  • Aortic Aneurysm, Abdominal / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Female
  • Gene Expression
  • Humans
  • Immunologic Memory / immunology
  • Interferon-gamma / analysis
  • Interferon-gamma / immunology
  • Interleukin-4 / immunology
  • Interleukins / immunology
  • Male
  • Middle Aged
  • Phenotype
  • T-Box Domain Proteins
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-bet Transcription Factor
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Transcription Factors / analysis
  • Transcription Factors / immunology

Substances

  • Antigens, CD
  • Interleukins
  • T-Box Domain Proteins
  • T-bet Transcription Factor
  • Transcription Factors
  • Interleukin-4
  • Interferon-gamma