Association of atherosclerosis with expression of the LILRB1 receptor by human NK and T-cells supports the infectious burden hypothesis

Arterioscler Thromb Vasc Biol. 2011 Oct;31(10):2314-21. doi: 10.1161/ATVBAHA.111.233288. Epub 2011 Aug 4.

Abstract

Objective: The contribution of human cytomegalovirus (HCMV) to vascular disease may depend on features of the immune response not reflected by the detection of specific antibodies. Persistent HCMV infection in healthy blood donors has been associated with changes in the distribution of NK cell receptors (NKR). The putative relationship among HCMV infection, NKR distribution, subclinical atherosclerosis, and coronary heart disease was assessed.

Methods and results: NKR expression was compared in acute myocardial infarction (AMI) patients (n=70) and a population-based control sample (n=209). The relationship between NKR expression and carotid intima-media thickness (CIMT) in controls (n=149) was also studied. HCMV infection was associated with higher proportions of NKG2C+ and LILRB1+ NK and T-cells. In contrast, only LILRB1+ NK and CD56+ T-cells were found to be increased in AMI patients, independent of age, sex, conventional vascular risk factors, and HCMV seropositivity. Remarkably, LILRB1 expression in NK and T-cells significantly correlated with CIMT in controls.

Conclusions: The association of overt and subclinical atherosclerotic disease with LILRB1+ NK and T-cells likely reflects a relationship between the immune challenge by infections and cardiovascular disease risk, without attributing a dominant role for HCMV. Our findings may lead to the identification of novel biomarkers of vascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood
  • Antigens, CD / blood*
  • CD56 Antigen / blood
  • Carotid Arteries / diagnostic imaging
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / immunology
  • Carotid Artery Diseases / virology*
  • Case-Control Studies
  • Chi-Square Distribution
  • Cross-Sectional Studies
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / complications*
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / immunology
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / virology*
  • Leukocyte Immunoglobulin-like Receptor B1
  • Linear Models
  • Male
  • Middle Aged
  • Myocardial Infarction / immunology
  • Myocardial Infarction / virology*
  • NK Cell Lectin-Like Receptor Subfamily C / blood
  • Receptors, Immunologic / blood*
  • Risk Assessment
  • Risk Factors
  • Spain
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology*
  • Tunica Intima / diagnostic imaging
  • Tunica Media / diagnostic imaging
  • Ultrasonography

Substances

  • Antibodies, Viral
  • Antigens, CD
  • CD56 Antigen
  • KLRC2 protein, human
  • LILRB1 protein, human
  • Leukocyte Immunoglobulin-like Receptor B1
  • NCAM1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, Immunologic