title: Relationship between cytomegalovirus (CMV) IgG serology, detectable CMV DNA in peripheral monocytes, and CMV pp65(495-503)-specific CD8+ T cells in older adults.
abstract: In immunocompetent individuals, cytomegalovirus (CMV) is thought to persist in a latent state in monocytes and myeloid progenitor cells, establishing a lifelong infection. In CMV-seropositive older adults, aging has been associated with both expansion of CMV pp65(495-503)-specific CD8(+) T cell clones and shrinkage of the T cell repertoire that characterize T cell immunosenescence. In fact it has been suggested that chronic CMV infection is a driving force in age-related T cell immunosenescence. In older adults, chronic CMV infection is conventionally diagnosed by positive IgG serology which does not distinguish between past and persistent infections. To better define the relationship between chronic CMV infection and expansion of CMV pp65(495-503)-specific CD8(+) T cells, we directly assessed CMV viral DNA in monocyte-enriched peripheral blood mononuclear cells in 16 HLA-A2-positive elderly volunteers (mean age = 83 years). While all participants had positive CMV IgG serology by enzyme-linked immunosorbent assays, only nine (56%) had detectable CMV DNA by nested polymerase chain reaction. These nine individuals had significantly higher percentages of CMV pp65(495-503) tetramer-positive CD8(+) T cells (median = 1.3%) than those without detectable CMV DNA (median = 0.1%; p < 0.001). Absolute CMV IgG antibody titers did not differ between these two groups (median = 54.6 vs 44.2 EU/ml, respectively, p = 0.4). CMV IgM titers were negative for all 16 participants, suggesting that recent primary CMV infection was unlikely. These results demonstrate a strong association between the presence of CMV DNA in peripheral monocytes and the expansion of CD8(+) T cells specific for the CMV immunodominant epitope pp65(495-503). Although the sample size in this study is relatively small, these findings provide initial evidence suggesting the heterogeneity of CMV IgG-seropositive older adult population and CMV viral DNA detection in peripheral monocytes as an informative tool to better understand the relationship between chronic CMV infection and T cell immunosenescence.
authors.affiliation: Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. sleng1@jhmi.edu
authors.forename: Sean X
authors.initials: SX
authors.lastname: Leng
authors.forename: Tao
authors.initials: T
authors.lastname: Qu
authors.forename: Richard D
authors.initials: RD
authors.lastname: Semba
authors.forename: Huifen
authors.initials: H
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Yao
authors.forename: Tricia
authors.initials: T
authors.lastname: Nilles
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Bhavish
authors.initials: B
authors.lastname: Manwani
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Walston
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Linda P
authors.initials: LP
authors.lastname: Fried
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: Jay H
authors.initials: JH
authors.lastname: Bream
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D004279:DNA, Viral / Q000032:analysis*; D018984:Epitopes, T-Lymphocyte; D005260:Female; D015789:HLA-A2 Antigen / Q000097:blood; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D009000:Monocytes / Q000821:virology*; D010750:Phosphoproteins / Q000276:immunology*; D016133:Polymerase Chain Reaction; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa