Abdominal aortic aneurysm (AAA) is a common disease with often life-threatening consequences. This vascular disorder is responsible for 1–2% of all deaths in men aged 65 years or older. Autoimmunity may be responsible for the pathogenesis of AAA. Although it is well documented that infiltrating T cells are essentially always present in AAA lesions, little is known about their role in the initiation and/or progression of the disease. To determine whether T cells infiltrating AAA lesions contain clonally expanded populations of T cells, we amplified β-chain TCR transcripts by the nonpalindromic adaptor–PCR/Vβ-specific PCR and/or Vβ-specific PCR, followed by cloning and sequencing. We report in this article that aortic abdominal aneurysmal lesions from 8 of 10 patients with AAA contained oligoclonal populations of T cells. Multiple identical copies of β-chain TCR transcripts were identified in these patients. These clonal expansions are statistically significant. These results demonstrate that αβ TCR+ T lymphocytes infiltrating aneurysmal lesions of patients with AAA have undergone proliferation and clonal expansion in vivo at the site of the aneurysmal lesion, in response to unidentified self- or nonself Ags. This evidence supports the hypothesis that AAA is a specific Ag–driven T cell disease.

To determine whether monoclonal/oligoclonal T cells are present in abdominal aortic aneurysm (AAA) lesions, we amplified beta-chain T cell receptor (TCR) transcripts from these lesions by the nonpalindromic adaptor (NPA)-polymerase chain reaction (PCR)/V-beta-specific PCR followed by cloning and sequencing. Sequence analysis revealed the presence of substantial proportions of identical beta-chain TCR transcripts in AAA lesions in 9 of 10 patients examined, strongly suggesting the presence of oligoclonal populations of alphabeta TCR+ T cells. We have also shown the presence of oligoclonal populations of gammadelta TCR+ T cells in AAA lesions. Sequence analysis after appropriate PCR amplification and cloning revealed the presence of substantial proportions of identical VgammaI and VgammaII TCR transcripts in 15 of 15 patients examined, and of Vdelta1 and Vdelta2 TCR transcripts in 12 of 12 patients. These clonal expansions were very strong. All these clonal expansions were statistically significant by the binomial distribution. In other studies, we determined that mononuclear cells infiltrating AAA lesions express early- (CD69), intermediate- (CD25, CD38), and late- (CD45RO, HLA class II) activation antigens. These findings suggest that active ongoing inflammation is present in the aortic wall of patients with AAA. These results demonstrate that oligoclonal alphabeta TCR+ and gammadelta TCR+T cells are present in AAA lesions. These oligoclonal T cells have been clonally expanded in vivo in response to yet unidentified antigens. Although the antigenic specificity of these T cells remains to be determined, these T cells may play a significant role in the initiation and/or the propagation of the AAA. It appears that AAA is a specific antigen-driven T cell disease.

Chronic cardiac allograft rejection presents pathologically as graft arteriosclerosis (GA) characterized by recipient T cell and monocyte infiltration. To determine whether oligoclonal T cells are present in coronary arteries of cardiac allografts from patients with GA, we conducted sequencing analysis of β-chain TCR transcripts from these explanted coronary arteries using the nonpalindromic adaptor-PCR. Substantial proportions of identical β-chain TCR transcripts in three of five patients were observed, clearly demonstrating the presence of oligoclonal T cells. TCR transcripts from the arteries of two other patients were relative heterogeneous. High proportions of identical CDR3 β-chain TCR motifs were found in each patient. GENEBANK/EMBL/SWISS PROT database comparison of all sequences revealed that these β-chain TCR transcripts were novel. Using Vβ-specific PCR (independent amplification), we found in patient GA03 that the TCR transcript that was clonally expanded in the left anterior descending artery after nonpalindromic adaptor-PCR was also clonally expanded in the right coronary artery of the same allograft. These results demonstrate that this TCR transcript was clonally expanded at different anatomic sides of the cardiac allograft in a systemic manner. In two patients identical β-chain TCR transcripts that were found to be clonally expanded in the coronary arteries of their explanted cardiac allografts were also found to be clonally explanted in endomyocardial biopsies collected 17 and 21 mo earlier from each patient. The presence of oligoclonal populations of T cells in the rejected graft suggest that these T cells have undergone specific Ag-driven proliferation and clonal expansion early on within the graft and persist throughout the post-transplantation period.

We have investigated the clonality of ␤-chain T-cell receptor (TCR) transcripts from the cerebrospinal fluid (CSF) and peripheral blood from a 7-year old child who developed a multiphasic disseminated encephalomyelitis following an infection with hepatitis A virus. We amplified ␤-chain TCR transcripts by nonpalindromic adaptor (

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