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-- and TNF--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- 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- 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.

Massive load of functional effector CD4+ and CD8+ T cells against cytomegalovirus in very old subjects / Vescovini, Rosanna; Biasini, C; Fagnoni, Ff; Telera, Ar; Zanlari, L; Pedrazzoni, Mario; Bucci, L; Monti, D; Medici, Maria Cristina; Chezzi, Carlo; Franceschi, C; Sansoni, Paolo. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 179(6):(2007), pp. 4283-4291.

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

VESCOVINI, Rosanna;PEDRAZZONI, Mario;MEDICI, Maria Cristina;CHEZZI, Carlo;SANSONI, Paolo
2007-01-01

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-- and TNF--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- 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- 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.
2007
Massive load of functional effector CD4+ and CD8+ T cells against cytomegalovirus in very old subjects / Vescovini, Rosanna; Biasini, C; Fagnoni, Ff; Telera, Ar; Zanlari, L; Pedrazzoni, Mario; Bucci, L; Monti, D; Medici, Maria Cristina; Chezzi, Carlo; Franceschi, C; Sansoni, Paolo. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 179(6):(2007), pp. 4283-4291.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2296115
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