Circulating pro-inflammatory CD4posCD28null T cells are independently associated with cardiovascular disease in ESRD patients

Nephrol Dial Transplant. 2010 Nov;25(11):3640-6. doi: 10.1093/ndt/gfq203. Epub 2010 Apr 16.

Abstract

Background: Cytomegalovirus seropositivity is associated with an increased risk for cardiovascular disease in end-stage renal disease (ESRD) patients. Circulating pro-inflammatory CD4posCD28null T cells are expanded in cytomegalovirus-seropositive ESRD patients and potentially could mediate atherosclerotic plaque instability and rupture.

Methods: In this study, we tested the hypothesis that increased numbers of circulating CD4posCD28null T cells may represent a risk factor for cardiovascular disease in ESRD patients. Prospectively collected data from 240 cytomegalovirus-seropositive stable ESRD patients were analysed.

Results: Traditional cardiovascular risk factors (age, smoking, hypercholesterolaemia and diabetes mellitus) and the percentage and absolute number of CD4posCD28null T cells were significantly associated with the presence of atherosclerotic disease, after univariate and multivariate statistical analysis. An ~2-3-fold increase in the prevalence of atherosclerotic disease was noted between patients with the highest and lowest number of CD4posCD28null cells. CD8posCD28null T-cell populations were also significantly expanded in cytomegalovirus-seropositive ESRD patients and closely correlated with the number of CD4posCD28null T cells. However, this cell population was not related to an increased prevalence of cardiovascular disease.

Conclusions: Cytomegalovirus-seropositive ESRD patients may have substantially increased numbers of circulating pro-inflammatory CD4posCD28null T cells that are independently associated with the presence of atherosclerotic disease. The expansion of these cells may therefore represent a novel non-traditional cardiovascular risk factor for ESRD patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Atherosclerosis / etiology
  • Atherosclerosis / immunology
  • CD28 Antigens / analysis*
  • CD4 Antigens / analysis*
  • Cardiovascular Diseases / etiology*
  • Cytomegalovirus Infections / complications
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / immunology
  • Male
  • Middle Aged
  • Risk Factors
  • T-Lymphocytes / physiology*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • CD28 Antigens
  • CD4 Antigens
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma