title: T-helper type 1 bias in healthy people is associated with cytomegalovirus serology and atherosclerosis: the Multi-Ethnic Study of Atherosclerosis.
abstract: BACKGROUND
  Although T-helper type 1 (Th1) cells are considered important in atherosclerosis, the relationships between Th1 and Th2 cells and atherosclerosis have not been examined in population-based studies.
  
  
  RESULTS
  We measured Th cells as a percentage of lymphocytes by flow cytometry using CD4 staining (%CD4) in 917 participants of the Multi-Ethnic Study of Atherosclerosis. We also measured interferon gamma-positive and interleukin-4-positive CD4(+) cells, representing Th1 and Th2 subpopulations (%Th1 and %Th2), respectively. We found that %CD4 was 1.5% lower per 10 years of age (P<0.0001). Whites had higher %CD4 and lower %Th1 and %Th2 values than other race/ethnic groups. Body mass index (BMI) and blood pressure were associated with %CD4, but no traditional cardiovascular disease (CVD) risk factors were associated with %Th1 or %Th2. In multivariable models, the major independent variable associated with %Th1 was cytomegalovirus (CMV) antibody titer, with minor contributions from age, sex, seasonality, and interleukin-6. In models with coronary artery calcification level as the outcome, significant independent variables included age, sex, smoking status, and %Th1 (β=0.25; P ≤ 0.01). Both %Th1 and %Th2 were associated with common carotid intimal media thickness (β=0.02 and -0.02, respectively; both P<0.05), as were age, sex, race/ethnicity, blood pressure, and BMI.
  
  
  CONCLUSIONS
  Th1 bias is associated with subclinical atherosclerosis in a multiethnic population. The main Th1 correlate was CMV infectious burden. These findings are consistent with a role of Th1 cells in atherosclerosis and suggest the importance of prospective studies of T-helper cell biasing in CVD.
authors.affiliation: Department of Pathology, University of Vermont, Burlington, VT 05446, USA. russell.tracy@uvm.edu
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Doyle
authors.forename: Nels C
authors.initials: NC
authors.lastname: Olson
authors.forename: Sally A
authors.initials: SA
authors.lastname: Huber
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.forename: Reem
authors.initials: R
authors.lastname: Sallam
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kronmal
mesh_terms: D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D050197:Atherosclerosis / Q000097:blood* / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D011446:Prospective Studies; D012698:Serologic Tests; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral
keywords: T‐helper cell; atherosclerosis; epidemiology; immunology; inflammation