Gamma/delta (γδ) T-cell receptor (TCR)-expressing T cells are clonally expanded in aneurysmal lesions of patients with abdominal aortic aneurism (AAA)

Abstract

Abstract Several lines of evidence strongly suggest that AAA is a specific antigen-driven T-cell inflammatory disease with a strong genetic component. We tested the hypothesis that γ- and δ-chain TCR transcripts are clonally expanded in AAA lesions. Previously, we showed clonally expanded α-chain (PloS One 2019;14:e0218990) and β-chain (J Immunol. 2014; 192:4897) TCR transcripts in AAA lesions of patients with AAA. We employed two-sided VγI-, VγII-, Vδ1- and Vδ2-specific PCR followed by cloning and sequencing of amplified transcripts to examine whether VγI-, VγII-, Vδ1- and Vδ2-TCR transcripts, respectively, were clonally expanded in aneurysmal lesions of patients with AAA. Clonally expanded VγI-, VγII-, Vδ1- and Vδ2-TCR transcripts were identified in AAA aneurysmal lesions. We identified multiple identical copies of: (i) VγI-TCR transcripts in 16 of 18 patients (range of identical transcripts 30% to 80% in individual patients); (ii) VγII-TCR transcripts in 15 of 15 patients (range of identical transcripts 39% to 80%);.(iii) Vδ1-TCR transcripts in 12 of 12 patients (range of identical transcripts 29% to 94%); and (iv) Vδ2-TCR transcripts in 10 of 10 patients (range of identical transcripts 40% to 91%). These results were statistically significant. PBMC from normal donors (methodological controls) contained almost exclusively unique VγI-, VγII- and Vδ2-TCR transcripts. In contrast, Vδ1 transcripts from PBMC from certain normal donors contained clonally expanded T cells, in agreement with previous reports. In conclusion, clonally expanded γδ TCR-expressing T cells were found in aneurysmal lesions of patients with AAA. These T cells may play an important role in the pathogenesis of AAA. Supported in part by grant RO1 HL64340 from NIH.