Abdominal Aortic Aneurysm Is a Specific Antigen‐Driven T Cell Disease

Abstract

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.

Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells

“…Also, inflammatory AAA contains numerous inflammatory cells arranged in follicles, suggesting a cellmediated Ag response (7). ii) Mononuclear cells infiltrating AAA lesions express early (CD69), intermediate (CD25, CD38), and late (CD45RO, HLA class II) activation Ags, demonstrating an active ongoing inflammatory response in these lesions (9). iii) AAA is associated with particular HLA alleles (10,11).…”

“…This is supported by the following. i) The presence of inflammatory mononuclear cell infiltrates in AAA lesions, consisting mostly of T and B cells, NK cells, and macrophages (7)(8)(9). These inflammatory infiltrates are particularly profound in the adventitia.…”

T lymphocytes and aortic aneurysms

“…Besides αβ T cells infiltration in aneurysms, γδ T cells are also present and play an important role in aneurysms [19]. Most of the infiltrating T cells in Takayasu's arteritis (TA), a chronic inflammation response with hallmark of stenosis or aneurysm of large elastic arteries, consist of gamma delta (γδ) T cells.…”

“…Immunohistochemical staining and flow cytometry suggested that elevated numbers of CD3 + cells (include both CD3 + TCRαβ + and CD3 + TCRγδ + cells), localizing in aortic media and adventitia, were present in aneurysm patients [16,17], which may further led to the death of VSMCs [18]. With the evidence that oligoclonal αβ TCR+T cell populations expansion in aneurysmal lesions from AAA patients, AAA is considered as a specific antigen-driven T cell disease [19,20]. The T cell co-stimulatory factors CD28 and CTLA-4, as well as their ligands CD80 and CD86 have been found in AAA patients, with sCD28 and sCD86 increased and sCTLA-4 decreased in plasma.…”

Etiology and Pathogenisis of Aortic Aneurysm

“…A small number of studies have concentrated on multiplex AAA families (with at least 2 affected members) (Platsoucas et al, 2006;Oleszak et al, 2004). Genome-wide scans of these patients have suggested a role for genes located on chromosome 19q13 and 4q31.47.…”