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A novel cytomegalovirus-induced regulatory-type t-cell subset increases in size during older life and links virus-specific immunity to vascular pathology

journal contribution
posted on 2023-06-08, 17:42 authored by Nadia Terrazzini, Martha Bajwa Joseph, Serena Vita, Elizabeth Cheek, David Thomas, Nabila Seddiki, Helen Smith, Florian KernFlorian Kern
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.

History

Publication status

  • Published

Journal

Journal of Infectious Diseases

ISSN

0022-1899

Publisher

Oxford University Press

Issue

9

Volume

209

Page range

1382-1392

Department affiliated with

  • Clinical and Experimental Medicine Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2014-07-02

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