Different contribution of EBV and CMV infections in very long-term carriers to age-related alterations of CD8+ T cells.
Aging is accompanied by a complex dynamics of CD8+ T cell subsets whose origin is unclear. To evaluate the impact of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) chronic infections on CD8+ T cells in far advanced age, we studied CD8+ T cells frequencies and phenotype in nonagenarians and centenarians by HLA-A*0201- and HLA-B*0702-tetramers incorporating epitopes specific of both viruses along with viral replication. The results demonstrate that EBV and CMV infections induce quantitatively and qualitatively different CD8+ T-cell responses in advanced aging. The frequency and absolute number of CD8+ T cells specific for one lytic and two latent EBV-epitopes, were relatively low and mostly included within CD8+ CD28+ cells. By contrast, CMV infection was characterized by highly variable numbers of CD8+ T cells specific for two differently restricted CMV-epitopes that, in some subjects, were strikingly expanded. Moreover, the great majority of anti-CMV CD8+ T cells did not bear CD28 antigen. Notwithstanding the expansion of CMV-specific CD8+ lymphocytes, CMV-DNA detection in blood samples was invariably negative. Altogether, we suggest that CMV, but not EBV, can sustain chronic activation of the HLA-class I restricted effector arm in elderly that might have detrimental effects on age-associated diseases.
Department of Internal Medicine and Biomedical Sciences, University of Parma, 43100 Parma, Italy.
Rosanna
R
Vescovini
Annarita
A
Telera
Francesco F
FF
Fagnoni
Claudia
C
Biasini
Maria Cristina
MC
Medici
Pierpaolo
P
Valcavi
Patricia
P
di Pede
Gianluca
G
Lucchini
Luca
L
Zanlari
Giovanni
G
Passeri
Franco
F
Zanni
Carlo
C
Chezzi
Claudio
C
Franceschi
Paolo
P
Sansoni
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002908:Chronic Disease; D003587:Cytomegalovirus / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000276:immunology*; D004279:DNA, Viral / Q000032:analysis; D000939:Epitopes / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007962:Leukocytes / Q000821:virology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000821:virology
D018106:CD28 Antigens; D004279:DNA, Viral; D000939:Epitopes; D015395:Histocompatibility Antigens Class I