A Novel Cytomegalovirus-Induced Regulatory-Type T-Cell Subset Increases in Size During Older Life and Links Virus-Specific Immunity to Vascular Pathology

Article


Terrazzini, N., Bajwa, Martha, Vita, Serena, Cheek, Elizabeth, Thomas, David, Seddiki, Nabila, Smith, Helen and Kern, Florian 2014. A Novel Cytomegalovirus-Induced Regulatory-Type T-Cell Subset Increases in Size During Older Life and Links Virus-Specific Immunity to Vascular Pathology. Journal of Infectious Diseases. 209 (9), pp. 1382-1392.
AuthorsTerrazzini, N., Bajwa, Martha, Vita, Serena, Cheek, Elizabeth, Thomas, David, Seddiki, Nabila, Smith, Helen and Kern, Florian
Abstract

Background. Cytomegalovirus (CMV) infection directly targets vascular endothelium and smooth muscle and at older ages is associated with accelerated vascular pathology and mortality. CMV-specific cellular immunity might directly contribute to this process.

Methods. Conventional ex vivo activation–induced T-cell responses to 19 dominant CMV antigens, along with CMV-specific inducible regulatory-type CD4+ T cells (iTregs), were measured in healthy older people, using a novel protocol that included classic Treg markers alongside the activation marker CD134. Measurements were correlated with diastolic, systolic, and mean arterial blood pressure, a surrogate marker for arterial stiffness.

Results. CMV-specific iTregs recognized the same antigens as conventional CD4+ T cells and were significantly more frequent at older ages. They suppressed antigen-specific and nonspecific proliferation and in large part expressed Foxp3. Frequencies of CMV-specific iTregs and CD8+ T cells (summated response) were significantly associated with diastolic and mean arterial pressures. Confounders, including age, body mass index, smoking, antihypertensive medication use, or C-reactive protein levels, did not explain these observations.

Conclusions. A novel CMV-induced regulatory-type CD4+ T-cell subset is readily detectable in CMV-infected people and, like the aggregate CD8+ T-cell response to the most dominant CMV antigens, is quantitatively associated with arterial stiffness in older life. Whereas CD8+ effector T cells might directly cause vascular injury, iTregs may attenuate this response.

JournalJournal of Infectious Diseases
Journal citation209 (9), pp. 1382-1392
ISSN1537-6613
0022-1899
Year2014
PublisherOxford University Press
Publisher's version
License
CC BY
Publisher's version
License
CC BY
Web address (URL)http://dx.doi.org/10.1093/infdis/jit576
Publication dates
Print2014
Publication process dates
Deposited13 Mar 2015
Accepted10 Sep 2013
FunderDunhill Medical Trust
Copyright information© The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Additional information

Presented in part at Federation of Clinical Immunology Societies 2012, Vancouver, Canada, 20–23 June 2012

LicenseCC BY 4.0
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