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

作者：Terrazzini Nadia^*; Bajwa Martha; Vita Serena; Cheek Elizabeth; Thomas David; Seddiki Nabila; Smith Helen; Kern Florian

来源：Journal of Infectious Diseases, 2014, 209(9): 1382-1392.

DOI：10.1093/infdis/jit576

• Arteriosclerosis
• infection
• immunology
• inflammation
• hypertension
• iTreg
• Regulatory T-Cells

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.

• 出版日期2014-5-1