The mammalian immune system defends the organism against pathogens, and possibly cancer, but is known to become dysregulated with increasing age. This results in greater morbidity and mortality due to infectious disease in old people. The most important changes occur in T cell immunity, manifested sometimes dramatically as altered clonal expansions of cells of limited antigen specificity and a marked shrinkage of the T cell antigen receptor repertoire. At the same time, it was independently reported that CMV seropositivity was associated with many of the same T cell changes that were being identified as biomarkers, of immune ageing. It has now become clear that CMV is commonly the driving force behind the oligoclonal expansions and altered phenotypes and functions of CD8 cells seen in most old people. These changes are much less obvious in centenarians and most extreme in people whom longitudinal studies have shown to possess an "immune risk profile". This is a cluster of immunological parameters of which CMV seropositivity is one component and which predicts incipient mortality in an elderly population. Taken together, these findings suggest the hypothesis that persistence of CMV as a chronic antigenic stressor is a major contributor to immunosenescence and associated mortality. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, EnglandJohn Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Appay, V
Zaunders, JJ
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Zaunders, JJ
Papagno, L
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Papagno, L
Sutton, J
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Sutton, J
Jaramillo, A
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Jaramillo, A
Waters, A
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Waters, A
Easterbrook, P
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Easterbrook, P
Grey, P
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Grey, P
Smith, D
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Smith, D
McMichael, AJ
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McMichael, AJ
Cooper, DA
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Cooper, DA
Rowland-Jones, SL
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Rowland-Jones, SL
Kelleher, AD
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
机构:
John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, EnglandJohn Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Appay, V
Zaunders, JJ
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Zaunders, JJ
Papagno, L
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Papagno, L
Sutton, J
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Sutton, J
Jaramillo, A
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Jaramillo, A
Waters, A
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Waters, A
Easterbrook, P
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Easterbrook, P
Grey, P
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Grey, P
Smith, D
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Smith, D
McMichael, AJ
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
McMichael, AJ
Cooper, DA
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Cooper, DA
Rowland-Jones, SL
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England
Rowland-Jones, SL
Kelleher, AD
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机构:John Radcliffe Hosp, Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England