Age-associated Epstein-Barr virus-specific T cell responses in seropositive healthy adults

Clin Exp Immunol. 2014 Jul;177(1):320-32. doi: 10.1111/cei.12337.

Abstract

Epstein-Barr virus (EBV) is present in 95% of the world's adult population. The immune response participates in immune vigilance and persistent infection control, and this condition is maintained by both a good quality (functionality) and quantity of specific T cells throughout life. In the present study, we evaluated EBV-specific CD4(+) and CD8(+) T lymphocyte responses in seropositive healthy individuals younger and older than 50 years of age. The assessment comprised the frequency, phenotype, functionality and clonotypic distribution of T lymphocytes. We found that in both age groups a similar EBV-specific T cell response was found, with overlapping numbers of tumour necrosis factor (TNF)-α(+) T lymphocytes (CD4(+) and CD8(+)) within the memory and effector cell compartments, in addition to monofunctional and multi-functional T cells producing interleukin (IL)-2 and/or interferon (IFN)-γ. However, individuals aged more than 50 years showed significantly higher frequencies of IL-2-producing CD4(+) T lymphocytes in association with greater production of soluble IFN-γ, TNF-α and IL-6 than subjects younger than 50 years. A polyclonal T cell receptor (TCR)-variable beta region (Vβ) repertoire exists in both age groups under basal conditions and in response to EBV; the major TCR families found in TNF-α(+) /CD4(+) T lymphocytes were Vβ1, Vβ2, Vβ17 and Vβ22 in both age groups, and the major TCR family in TNF-α(+) /CD8(+) T cells was Vβ13·1 for individuals younger than 50 years and Vβ9 for individuals aged more than 50 years. Our findings suggest that the EBV-specific T cell response (using a polyclonal stimulation model) is distributed throughout several T cell differentiation compartments in an age-independent manner and includes both monofunctional and multi-functional T lymphocytes.

Keywords: EBV-specific memory and effector T lymphocytes; TCR-Vβ repertoire; flow cytometry; multi-functional T lymphocytes; soluble cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood
  • Antigens, Viral / immunology
  • Asymptomatic Diseases
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Clone Cells
  • Colombia
  • Epstein-Barr Virus Infections / epidemiology
  • Epstein-Barr Virus Infections / immunology*
  • Female
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / virology
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Interleukin-2
  • Receptors, Antigen, T-Cell, alpha-beta
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma