CMV latent infection improves CD8+ T response to SEB due to expansion of polyfunctional CD57+ cells in young individuals

PLoS One. 2014 Feb 12;9(2):e88538. doi: 10.1371/journal.pone.0088538. eCollection 2014.

Abstract

Cytomegalovirus (CMV) latent infection has a deleterious effect on the efficacy of influenza vaccination in the elderly, suggesting that CMV restricts immunological diversity impairing the immune system functionality in old age. Polyfunctional T cells produce multiple cytokines and higher amounts than mono-functional T cells. High number of polyfunctional T cells correlates with better prognosis during infection. Thus, the efficiency of T cell response associates with quality (polyfunctionality) rather than with quantity (percentage of T cells). We analyze the effect of CMV infection on CD8+ T cells polyfunctionality --degranulation (CD107a), IFN-gamma and TNF-alpha production--, from young CMV-seropositive and CMV-seronegative individuals and in middle age CMV-seropositive donors, in response to Staphylococcal Enterotoxin B (SEB). Our results show a higher percentage of polyfunctional CD8+ T cells in young CMV-seropositive individuals compared to CMV-seronegative. Also, we find an expansion of CD8+CD57+ T cells in CMV-seropositive individuals, which are more polyfunctional than CD8+CD57- cells. In middle age individuals there is a higher frequency of SEB-responding CD8+ T cells, mainly TNF-alpha or TNF-alpha/IFN-gamma producers, whereas the percentage of polyfunctional cells (IFN-gamma/TNF-alpha/CD107a) is similar to the percentages found in young CMV-seropositive. Therefore, whereas it has been shown that CMV latent infection can be detrimental for immune response in old individuals, our results indicate that CMV-seropositivity is associated to higher levels of polyfunctional CD8+ T cells in young and middle age donors. This increase in polyfunctionality, which can provide an immunological advantage in the response to other pathogens, is due to a CD8+CD57+ T cell expansion in CMV-seropositive individuals and it is independent of age. Conversely, age could contribute to the inflammation found in old individuals by increasing the percentage of cells producing pro-inflammatory cytokines. These findings highlight the necessity of further studies on the benefits/detrimental effects of CMV infection in the response to vaccination and other infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • CD3 Complex / metabolism
  • CD57 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytomegalovirus Infections / immunology*
  • Enterotoxins / chemistry
  • Female
  • Flow Cytometry
  • Gene Expression Regulation
  • Humans
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / cytology
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Male
  • Middle Aged
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • CD3 Complex
  • CD57 Antigens
  • Enterotoxins
  • Lysosomal-Associated Membrane Protein 1
  • Tumor Necrosis Factor-alpha
  • enterotoxin B, staphylococcal
  • Interferon-gamma

Grant support

This study has been supported by the Instituto de Salud Carlos III, Ministry of Economy and Competitiveness (FIS Ref PS09/00723), SAF2009-09711 from the Ministry of Education and Science of Spain,GRU10104 (to RT) from Junta de Extremadura (Spain) and grants to INPATT research group from University of Extremadura, co-financed by the European Regional Development Fund (FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.