Massive load of functional effector CD4+ and CD8+ T cells against cytomegalovirus in very old subjects.
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-gamma- and TNF-alpha-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-gamma 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-gamma 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.
Vescovini
Rosanna
R
Department of Internal Medicine and Biomedical Sciences, University of Parma, Parma, Italy.
Biasini
Claudia
C
Fagnoni
Francesco F
FF
Telera
Anna Rita
AR
Zanlari
Luca
L
Pedrazzoni
Mario
M
Bucci
Laura
L
Monti
Daniela
D
Medici
Maria Cristina
MC
Chezzi
Carlo
C
Franceschi
Claudio
C
Sansoni
Paolo
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D003587:Cytomegalovirus / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D010455:Peptides / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014763:Viral Matrix Proteins / Q000502:physiology; D014764:Viral Proteins / Q000502:physiology