Cytomegalovirus Infection- and Age-Dependent Changes in Human CD8 + T-Cell Cytokine Expression Patterns

Abstract

T cells are strongly affected by immune aging, a phenomenon that leads to increased susceptibility to infections and decreased vaccination efficacy in elderly individuals. Cytomegalovirus (CMV) infection induces vigorous T-cell immune responses in humans and is thought to be a driving force of immune aging. In the present study we analyzed CMV-induced quantitative and qualitative differences in the cytokine-expressing T-cell repertoire from individuals of different age groups after in vitro stimulation. The CMV pp65 peptide pool and the superantigen Staphylococcus enterotoxin B (SEB) induced higher proportions of CD8+ effector T cells expressing gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor in the oldest study group, while only SEB induced increased responses in the middle-aged study group. Notably, CMV-specific multiple cytokine expression patterns revealed higher proportions of IFN-gamma- and TNF-alpha-coexpressing CD8+ T cells exclusively in the oldest study group. These qualitative differences were absent in SEB-induced CD8+ effector T cells, although quantitative differences were detected. We report age-dependent qualitative changes in CMV-specific CD8+ T-cell cytokine patterns which are biocandidate markers of immune exhaustion in elderly individuals.