title: Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals.
abstract: The deterioration in immune function with aging is thought to make a major contribution to the increased morbidity and mortality from infectious disease in old age. One aspect of immune senescence is the reduction in CD8 T cell repertoire as due to the accumulation of oligoclonal, memory T cells and a reduction in the naive T cell pool. CD8 T cell clonal expansions accumulate with age, but their antigenic specificity remains unknown. In this study, we show that in elderly individuals seropositivity for human CMV leads to the development of oligoclonal populations of CMV-specific CTL that can constitute up to one-quarter of the total CD8 T cell population. Furthermore, CMV-specific CTL have a highly polarized membrane phenotype that is typical of effector memory cells (CD28(-), CD57(+), CCR7(-)). TCR analyses show that CMV-specific CTL have highly restricted clonality with greater restriction in the larger expansions. Clonal analysis of the total CD8 T cell repertoire was compared between CMV-seropositive and CMV-seronegative donors. Thirty-three percent more clonal expansions were observed in CMV-seropositive donors in comparison with seronegative individuals. These data implicate CMV as a major factor in driving oligoclonal expansions in old age. Such a dramatic accumulation of virus-specific effector CTL might impair the ability to respond to heterologous infection and may underlie the negative influence of CMV seropositivity on survival in the very elderly.
authors.affiliation: Cancer Research U.K. Institute for Cancer Studies and Department of Geriatric Medicine, University of Birmingham, Edgbaston, United Kingdom.
authors.forename: Naeem
authors.initials: N
authors.lastname: Khan
authors.forename: Naseer
authors.initials: N
authors.lastname: Shariff
authors.forename: Mark
authors.initials: M
authors.lastname: Cobbold
authors.forename: Rachel
authors.initials: R
authors.lastname: Bruton
authors.forename: Jenni A
authors.initials: JA
authors.lastname: Ainsworth
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Sinclair
authors.forename: Laxman
authors.initials: L
authors.lastname: Nayak
authors.forename: Paul A H
authors.initials: PA
authors.lastname: Moss
mesh_terms: D000368:Aged; D000375:Aging / Q000276:immunology*; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D019672:Genes, T-Cell Receptor; D006801:Humans; D007156:Immunologic Memory; D008875:Middle Aged; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D018076:DNA, Complementary; D000939:Epitopes; D009842:Oligopeptides; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa