Abdominal aortic aneurysm is a specific antigen-driven T cell disease

Area of Science:

• Immunology
• Vascular Biology
• Genetics

Background:

• Abdominal aortic aneurysm (AAA) is a life-threatening condition characterized by aortic wall inflammation.
• The role of T cells in AAA pathogenesis is not fully understood.
• Investigating T cell populations within AAA lesions can provide insights into disease mechanisms.

Purpose of the Study:

• To determine the presence and clonality of T cells within human abdominal aortic aneurysm lesions.
• To characterize the T cell receptor (TCR) repertoire in AAA.
• To explore the implications of T cell clonal expansion in AAA pathogenesis.

Main Methods:

• Amplification of beta-chain T cell receptor (TCR) transcripts using nonpalindromic adaptor (NPA)-polymerase chain reaction (PCR) and V-beta-specific PCR.
• Cloning and sequencing of TCR transcripts from AAA lesions.
• Analysis of gamma-delta TCR transcripts (VgammaI, VgammaII, Vdelta1, Vdelta2) using PCR, cloning, and sequencing.
• Immunophenotyping of mononuclear cells in AAA lesions for activation markers (CD69, CD25, CD38, CD45RO, HLA class II).

Main Results:

• Substantial proportions of identical beta-chain TCR transcripts were found in 9 of 10 AAA patients, indicating oligoclonal alpha-beta T cells.
• Oligoclonal gamma-delta T cells were identified in all 15 patients examined (VgammaI, VgammaII) and 12 of 12 patients (Vdelta1, Vdelta2).
• Mononuclear cells in AAA lesions expressed activation antigens, suggesting active inflammation.

Conclusions:

• Oligoclonal alpha-beta and gamma-delta T cells are significantly present in abdominal aortic aneurysm lesions.
• These T cells exhibit clonal expansion in vivo, likely in response to unidentified antigens.
• AAA may be an antigen-driven T cell disease, with these T cells potentially contributing to its initiation and progression.