Intense antiextracellular adaptive immune response to human cytomegalovirus in very old subjects with impaired health and cognitive and functional status.
Human aging is characterized by expanded and altered adaptive immune responses to human CMV (HCMV). It is unclear whether this expansion has its origins in age-related homeostatic disturbances or viral reactivation, whether anti-CMV immune surveillance may still be effective, and what are the consequences of this expanded immune response for health and longevity. We conducted an observational cross-sectional study in groups of HCMV-seropositive subjects aged >or=65 y of variable health status to compare the intensity of Ab responses against HCMV with those against EBV and with CD4(+) and CD8(+) T cell proinflammatory effector responses directed to HCMV-derived pp65 and immediate-early protein 1 synthetic peptides. Ab responses to HCMV, but not to EBV, and anti-HCMV CD4(+), but not CD8(+), T cell responses were more intense in elderly subjects aged >or=85 y in poor health and were inversely correlated with markers of functional activity and cognitive function. Therefore, humoral and CD4(+) T cell anti-HCMV responses were specifically intensified in advanced aging associated with comorbidity and cognitive and functional impairments. Such a distinctive pattern of adaptive immunity indicates that immune responses targeting the extracellular phase of HCMV are increased in these elderly subjects and could represent an indirect effect of localized and undetectable HCMV reactivation. This study demonstrates that the oldest subjects in poor health with physical and mental impairment express intense functional immune responses to extracellular HCMV and suggests that they may be at risk for direct pathogenic effects by HCMV reactivation as well as indirect pathogenic effects linked to proinflammatory anti-HCMV effector responses.
Vescovini
Rosanna
R
Department of Internal Medicine and Biomedical Sciences, University of Parma,Parma, Italy. rosanna.vescovini@unipr.it
Biasini
Claudia
C
Telera
Anna Rita
AR
Basaglia
Manuela
M
Stella
Adriano
A
Magalini
Francesca
F
Bucci
Laura
L
Monti
Daniela
D
Lazzarotto
Tiziana
T
Dal Monte
Paola
P
Pedrazzoni
Mario
M
Medici
Maria Cristina
MC
Chezzi
Carlo
C
Franceschi
Claudio
C
Fagnoni
Francesco F
FF
Sansoni
Paolo
P
D056704:Adaptive Immunity; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000096:biosynthesis; D010054:Brief Psychiatric Rating Scale; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D003072:Cognition Disorders / Q000453:epidemiology / Q000276:immunology* / Q000523:psychology*; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003587:Cytomegalovirus / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005110:Extracellular Space / Q000276:immunology* / Q000821:virology*; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000138:chemical synthesis / Q000276:immunology; D018836:Inflammation Mediators / Q000502:physiology; D008297:Male; D010750:Phosphoproteins / Q000138:chemical synthesis / Q000276:immunology; D014763:Viral Matrix Proteins / Q000138:chemical synthesis / Q000276:immunology; D014775:Virus Activation / Q000276:immunology
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D018836:Inflammation Mediators; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa