Massive load of functional effector CD4+ and CD8+ T cells against cytomegalovirus in very old subjects

Rosanna Vescovini, Claudia Biasini, Francesco F. Fagnoni, Anna Rita Telera, Luca Zanlari, Mario Pedrazzoni, Laura Bucci, Daniela Monti, Maria Cristina Medici, Carlo Chezzi, Claudio Franceschi, Paolo Sansoni

Research output: Contribution to journalArticlepeer-review

Abstract

A progressive, systemic, and low-grade proinflammatory status is one of the major characteristics of immunosenescence. Emerging data suggest a possible contribution of CMV, known to chronically infect a large proportion of humans, lifelong from newborns to centenarians. To test this hypothesis, we evaluated functional T cell responses to two CMV immunogenic proteins, pp65 and IE-1, in 65 chronically infected subjects aged 25-100 years. PBMC were stimulated with mixtures of peptides spanning the entire sequence of both proteins, and Ag specificity and magnitude of intracellular IFN-γ- and TNF-α-positive cells were then analyzed within both CD4+ and CD8+ T cells. Results indicate that pp65 and, to a lesser extent, IE-1 constitute major Ags against which aged people target functionally efficient T cell effector responses with massive production of Th1 cytokines and exhibition of CD107a degranulation marker. As a result, the production of IFN-γ induced in T cells by both Ags was seven to eight times greater in very old than in young subjects. The comparative analysis of pp65-specific responses in these very long-term carriers revealed a reciprocal relationship between CD4+ and CD8+ producing IFN-γ in the same individuals. These results indicate that CMV represents an important pathogen responsible for a strong immune activation in human aging. Such a remarkable burden of effector CD4 + and CD8+ T cells may be necessary to protect the elderly from CMV endogenous reactivation, but can turn detrimental by giving a substantial contribution to the proinflammatory status that accompanies the main age-related diseases.

Original languageEnglish
Pages (from-to)4283-4291
Number of pages9
JournalJournal of Immunology
Volume179
Issue number6
Publication statusPublished - Sep 15 2007

ASJC Scopus subject areas

  • Immunology

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