Arterial Stiffness Is Associated With Cytomegalovirus‐Specific Senescent CD8 + T Cells

Author:

Yu Hee Tae12,Youn Jong‐Chan13,Kim Jong Hoon1,Seong Yeon‐Jae1,Park Su‐Hyung4,Kim Hyeon Chang5,Lee Won‐Woo6,Park Sungha2,Shin Eui‐Cheol1

Affiliation:

1. Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea

2. Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea

3. Division of Cardiology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea

4. Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea

5. Department of Preventive Medicine, Cardiovascular and Metabolic Diseases Etiology Research Center, Yonsei University College of Medicine, Seoul, Korea

6. Department of Microbiology and Immunology and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea

Abstract

Background Arterial stiffness is a well‐known predictor of future cardiovascular events. Search for the underlying mechanism of arterial stiffening is still under way. We investigated the relationship between arterial stiffness and cytomegalovirus infection in terms of T‐cell senescence. Methods and Results Arterial stiffness was evaluated using pulse wave velocity measurements in 415 Koreans (age 59±12 years). We also investigated the frequency of CD 57 + or CD 28 null senescent T cells in peripheral blood lymphocytes and analyzed which immune parameters were correlated with pulse wave velocity. Furthermore, cytomegalovirus‐specific T cells were stimulated with overlapping peptides covering pp65 protein, and T‐cell function was evaluated by intracellular cytokine staining of interferon‐γ, tumor necrosis factor‐α, and CD 107a. In a multivariate analysis, it was found that the frequency of CD 57 + cells in the CD 8 + T‐cell subset was independently correlated with pulse wave velocity after adjusting for traditional cardiovascular risk factors such as age, sex, diabetes mellitus history, smoking history, body mass index, blood pressure, serum creatinine, high‐density lipoprotein cholesterol, and high‐sensitivity C‐reactive protein. Cytomegalovirus pp65‐specific T cells were more frequently observed in the CD 8 + CD 57 + population than in the CD 8 + CD 57 population, and multivariate analysis revealed that the frequency of cytomegalovirus pp65‐specific interferon‐γ + , tumor necrosis factor‐α + , or CD 107a + cells in the CD 8 + T‐cell subset was independently correlated with pulse wave velocity as well. Conclusions We demonstrate that arterial stiffness is associated with senescent CD 57 + T cells and CMV pp65‐specific T cells in the CD 8 + T‐cell subset. The precise role of cytomegalovirus‐specific, senescent T cells in vascular aging needs to be further investigated.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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