title: A novel cytomegalovirus-induced regulatory-type T-cell subset increases in size during older life and links virus-specific immunity to vascular pathology.
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.
authors.affiliation: Division of Medicine.
authors.forename: Nadia
authors.initials: N
authors.lastname: Terrazzini
authors.forename: Martha
authors.initials: M
authors.lastname: Bajwa
authors.forename: Serena
authors.initials: S
authors.lastname: Vita
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cheek
authors.forename: David
authors.initials: D
authors.lastname: Thomas
authors.forename: Nabila
authors.initials: N
authors.lastname: Seddiki
authors.forename: Helen
authors.initials: H
authors.lastname: Smith
authors.forename: Florian
authors.initials: F
authors.lastname: Kern
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology; D001794:Blood Pressure / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D014652:Vascular Diseases / Q000097:blood / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD
keywords: Arteriosclerosis; Regulatory T-Cells; hypertension; iTreg; immunology; infection; inflammation