Dataset Information

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

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 CD57⁺ or CD28^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-?, tumor necrosis factor-?, and CD107a. In a multivariate analysis, it was found that the frequency of CD57⁺ cells in the CD8⁺ 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 CD8⁺CD57⁺ population than in the CD8⁺CD57^- population, and multivariate analysis revealed that the frequency of cytomegalovirus pp65-specific interferon-?⁺, tumor necrosis factor-?⁺, or CD107a⁺ cells in the CD8⁺ T-cell subset was independently correlated with pulse wave velocity as well.

Conclusions

We demonstrate that arterial stiffness is associated with senescent CD57⁺ T cells and CMV pp65-specific T cells in the CD8⁺ T-cell subset. The precise role of cytomegalovirus-specific, senescent T cells in vascular aging needs to be further investigated.

SUBMITTER: Yu HT

PROVIDER: S-EPMC5634298 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Arterial Stiffness Is Associated With Cytomegalovirus-Specific Senescent CD8<sup>+</sup> T Cells.

Yu Hee Tae HT Youn Jong-Chan JC Kim Jong Hoon JH Seong Yeon-Jae YJ Park Su-Hyung SH Kim Hyeon Chang HC Lee Won-Woo WW Park Sungha S Shin Eui-Cheol EC

Journal of the American Heart Association 20170828 9

<h4>Background</h4>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.<h4>Methods and results</h4>Arterial stiffness was evaluated using pulse wave velocity measurements in 415 Koreans (age 59±12 years). We also investigated the frequency of CD57<sup>+</sup> or CD28<sup>nul ...[more]

PMID: 28847915

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Project description:CD8+ cytotoxic T lymphocytes (CTLs) exert potent antiviral activity after HIV/SIV infection. However, efforts to harness the antiviral efficacy of CTLs for HIV/SIV prophylaxis and therapy have been severely hindered by two major problems: viral escape and exhaustion. By contrast, CTLs directed against human cytomegalovirus (HCMV), a ubiquitous chronic herpesvirus, seldom select for escape mutations and remain functional and refractory to exhaustion during chronic HCMV and HIV infection. Recently, attempts have been made to retarget HCMV-specific CTLs for cancer immunotherapy. We speculate that such a strategy may also be beneficial in the context of HIV/SIV infection, facilitating CTL-mediated control of HIV/SIV replication. As a preliminary assessment of the validity of this approach, we investigated the phenotypes and functionality of rhesus CMV (RhCMV)-specific CTLs in SIVmac239-infected Indian rhesus macaques (RMs), a crucial HIV animal model system. We recently identified two immunodominant, Mamu-A∗02-restricted CTL epitopes derived from RhCMV proteins and sought to evaluate the phenotypic and functional characteristics of these CTL populations in chronic SIVmac239 infection. We analyzed and directly compared RhCMV- and SIVmac239-specific CTLs during SIVmac239 infection in a cohort of Mamu-A∗01 + and Mamu-A∗02 + RMs. CTL populations specific for at least one of the RhCMV-derived CTL epitopes were detected in ten of eleven Mamu-A∗02 + animals tested, and both populations were detected in five of these animals. Neither RhCMV-specific CTL population exhibited significant changes in frequency, memory phenotype, granzyme B expression, exhaustion marker (PD-1 and CTLA-4) expression, or polyfunctionality between pre- and chronic SIVmac239 infection timepoints. In chronic SIVmac239 infection, RhCMV-specific CTLs exhibited higher levels of granzyme B expression and polyfunctionality, and lower levels of exhaustion marker expression, than SIVmac239-specific CTLs. Additionally, compared to SIVmac239-specific CTLs, greater proportions of RhCMV-specific CTLs were of the terminally differentiated effector memory phenotype (CD28- CCR7-) during chronic SIVmac239 infection. These results suggest that, in contrast to SIVmac239-specific CTLs, RhCMV-specific CTLs maintain their phenotypes and cytolytic effector functions during chronic SIVmac239 infection, and that retargeting RhCMV-specific CTLs might be a promising SIV immunotherapeutic strategy.

Dataset Information

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

Background

Methods and results

Conclusions

Publications

Arterial Stiffness Is Associated With Cytomegalovirus-Specific Senescent CD8<sup>+</sup> T Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Methods and results

Conclusions

Publications

Arterial Stiffness Is Associated With Cytomegalovirus-Specific Senescent CD8<sup>+</sup> T Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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