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-␥), tumor necrosis factor alpha (TNF-␣), 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-␥-and TNF-␣-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.

The Polyfunctionality of Human Memory CD8+ T Cells Elicited by Acute and Chronic Virus Infections Is Not Influenced by Age

“…It has been proposed that chronic CMV infection may drive immune senescence due to repeated oligoclonal expansions of CMV-specific CD8+ T cells leading to overpopulation of the memory T cell pool [7], [11], [23], [24], [25] and ultimately limiting the ability of the aging individual to combat previously encountered or novel viral infections [25]. However, a recent report has suggested that the size of the CD8+ T cell compartment may increase with age to accommodate expanding memory T cell populations without depleting CD8+ T cells with other specificities [26].…”

Cytomegalovirus-Induced Expression of CD244 after Liver Transplantation Is Associated with CD8+ T Cell Hyporesponsiveness to Alloantigen

“…However, several previously published observations in humans support our findings. First, CMV infection leads to T cell senescence and, thereby, impairs T cell responses to other Ags and to vaccinations (34,40,(49)(50)(51). Interestingly, CMV infection after LTx is associated with an increased predisposition to develop opportunistic infections (52).…”

Chronic Viral Infections and Immunosenescence, with a Focus on CMV

“…However, the vast majority of CMV-specific T cells, even in the elderly, are fully functional, secreting IFN-γ and TNF α in response to antigen, and are capable of cytotoxicity. In fact, the total IFN-γ and TNF α response to CMV antigens was higher in the elderly than in a middle aged group [49].…”