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

Terrazzini, Nadia, Bajwa Joseph, 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. ISSN 0022-1899

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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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical Medicine
Subjects: R Medicine
Depositing User: Sandy Gray
Date Deposited: 02 Jul 2014 07:41
Last Modified: 02 Jul 2014 07:41
URI: http://sro.sussex.ac.uk/id/eprint/49147
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