Decreased proportion of cytomegalovirus specific CD8 T-cells but no signs of general immunosenescence in Alzheimer's disease

PLoS One. 2013 Oct 14;8(10):e77921. doi: 10.1371/journal.pone.0077921. eCollection 2013.

Abstract

Cytomegalovirus (CMV) has been suggested as a contributing force behind the impaired immune responsiveness in the elderly, with decreased numbers of naïve T-cells and an increased proportion of effector T-cells. Immunological impairment is also implicated as a part of the pathogenesis in Alzheimer's disease (AD). The aim of this study was to investigate whether AD patients present with a different CMV-specific CD8 immune profile compared to non-demented controls. Blood samples from 50 AD patients and 50 age-matched controls were analysed for HLA-type, CMV serostatus and systemic inflammatory biomarkers. Using multi-colour flow cytometry, lymphocytes from peripheral blood mononuclear cells were analysed for CMV-specific CD8 immunity with MHC-I tetramers A01, A02, A24, B07, B08 and B35 and further classified using CD27, CD28, CD45RA and CCR7 antibodies. Among CMV seropositive subjects, patients with AD had significantly lower proportions of CMV-specific CD8 T-cells compared to controls, 1.16 % vs. 4.13 % (p=0.0057). Regardless of dementia status, CMV seropositive subjects presented with a lower proportion of naïve CD8 cells and a higher proportion of effector CD8 cells compared to seronegative subjects. Interestingly, patients with AD showed a decreased proportion of CMV-specific CD8 cells but no difference in general CD8 differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / immunology*
  • Aging / pathology
  • Alzheimer Disease / immunology*
  • Alzheimer Disease / pathology*
  • Antigens, CD / metabolism
  • CD4-CD8 Ratio
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology*
  • Case-Control Studies
  • Cell Differentiation / immunology
  • Cytomegalovirus / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Receptors, CCR7 / metabolism

Substances

  • Antigens, CD
  • CCR7 protein, human
  • Receptors, CCR7

Grants and funding

This work was funded by grants from The Family Ohlinder-Nielsen’s Foundation, Uppsala University, Landstinget i Uppsala län, Swedish Research Council (2006-2822, 2006-6326 and 2006-3464), Swedish Brain Foundation, Swedish Alzheimer Foundation and Swedish Society of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.