P-028 - CLONALLY EXPANDED GAMMA/DELTA (G?) T-CELL RECEPTOR (TCR)-POSITIVE T CELLS ARE PRESENT IN ANEURYSMAL LESIONS OF PATIENTS WITH ABDOMINAL AORTIC ANEURISM (AAA)

TOPIC:
Abdominal Aortic Aneurysms
AUTHORS:
Nwaneshiudu I. (Department of Microbiology and Immunology, Temple University School of Medicine ~ Philadelphia ~ United States of America) , White J. (Department of Surgery, Advocate Lutheran General Hospital and University of Illinois School of Medicine ~ Park Ridge ~ United States of America) , Lu S. (Department of Microbiology and Immunology, Temple University School of Medicine ~ Philadelphia ~ United States of America) , Nwaneshiudu A. (Department of Microbiology and Immunology, Temple University School of Medicine ~ Philadelphia ~ United States of America) , Solomides C. (Thomas Jefferson University Hospital ~ Philadelphia ~ United States of America) , Gaughan J. (Department of Medicine, Cooper University Hospital, and School of Medicine. Rowan University ~ Camden ~ United States of America) , Monos D. (Department of Pediatrics, University of Pennsylvania School of Medicine and Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia ~ Philadelphia ~ United States of America) , Oleszak E. (Department of Anatomy and Cellular Biology, Temple University School of Medicine ~ Philadelphia ~ United States of America) , Platsoucas C. (Department of Microbiology and Immunology, Temple University School of Medicine ~ Philadelphia ~ United States of America)
Introduction:
Evidence has been accumulated suggesting that AAA is a complex specific antigen-driven T-cell autoimmune disease with a strong genetic component. We have examined the hypothesis that γ- and δ-chain TCR transcripts are clonally expanded in AAA lesions. Previously, we have demonstrated the presence of clonally expanded α-chain and β-chain TCR transcripts in AAA lesions of patients with AAA (1-3).
Methods:
RNA was isolated from AAA surgical specimens, cDNA was synthesized and VγI-, VγII-, Vδ1- and Vδ2-chain TCR transcripts were amplified by two-sided VγI-, VγII-, Vδ1- and Vδ2-chain specific PCR, followed by cloning and sequencing of the amplified transcripts.
Results:
Clonally expanded VγI-, VγII-, Vδ1- and Vδ2-TCR transcripts were identified in AAA aneurysmal lesions. Statistically significant by the binomial distribution multiple identical copies of: (1) VγI-TCR transcripts were found in AAA lesions of 16 of 18 patients examined. The range of the identical VγI transcripts in individual patients was 30% to 80%; (2) VγII-TCR transcripts were found in AAA lesions of 15 of 15 patients examined. The range of identical VγII transcripts in individual patients was 39% to 80%; (3) Vδ1-TCR transcripts were found in AAA lesions of 12 of 12 patients examined. The range of identical Vδ1transcripts in individual patients was 29% to 94%; and (4) Vδ2-TCR transcripts were found in AAA lesions of 10 of 10 patients examined. The range of identical Vδ2 transcripts in individual patients was 40% to 91%. Peripheral blood mononuclear cells (PBMC) from normal donors were used as methodological controls and were comprised almost exclusively of 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.
Conclusion:
Clonally expanded γδ TCR T cells were identified in AAA lesions of patients with AAA and they may play an important role in the pathogenesis of the disease.
References:
(1) Platsoucas CD, Lu S, Nwaneshiudu I, Solomides C, Agelan A, Ntaoula N, Purev E, Li LP, Kratsios P, Mylonas E, Jung WJ, Evans K, Roberts S, Lu Y, Layvi R, Lin WL, Zhang X, Gaughan J, Monos DS, Oleszak EL, White JV. Abdominal aortic aneurysm is a specific antigen-driven T cell disease. Ann N Y Acad Sci. 2006;1085:224-35. (2) Lu S, White JV, Lin WL, Zhang X, Solomides C, Evans K, Ntaoula N, Nwaneshiudu I, Gaughan J, Monos D, Oleszak E, Platsoucas CD. Aneurysmal lesions of patients with abdominal aortic aneurysm contain clonally expanded T cells. J Immunol. 2014;192(10):4897-912. (3) Lu S, White JV, Judy RI, Merritt LL, Lin WL, Zhang X, Solomides C, Nwaneshiudu I, Gaughan J, Monos DS, Oleszak EL, Platsoucas CD. Clonally expanded alpha-chain T-cell receptor (TCR) transcripts are present in aneurysmal lesions of patients with Abdominal Aortic Aneurysm (AAA). PLoS One. 2019;14(7):e0218990.