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Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly.
Hadrup, Sine Reker; Strindhall, Jan; Køllgaard, Tania; Seremet, Tina; Johansson, Boo; Pawelec, Graham; thor Straten, Per; Wikby, Anders.
Afiliação
  • Hadrup SR; Tumor Immunology Group, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark. sir@cancer.dk
J Immunol ; 176(4): 2645-53, 2006 Feb 15.
Article em En | MEDLINE | ID: mdl-16456027
ABSTRACT
The age-associated decrease in functionality of the human immune system is thought to have a negative impact on the capacity to provide protection against infection, in turn leading to increased incidence of mortality. In a previous longitudinal study of octogenarians, we identified an immune risk phenotype (IRP) in the very elderly defined by an inverted CD4/CD8 ratio, which was associated with increased mortality and persistent CMV infection. In this study, we analyzed the CD8 clonal composition of nonagenarians and middle-aged individuals. An increased number of CD8 T cell clones was observed in the nonagenarians, and was associated with CMV-seropositivity. Surprisingly, CMV-seropositive nonagenarians with the IRP had a significantly lower number of clones compared with non-IRP individuals. The decrease in clone numbers in IRP individuals was associated with shorter survival time. MHC/peptide multimer staining indicated that the frequency of CMV-specific T cells was higher in nonagenarians than in the middle-aged, but the ratio of functionally intact cells was significantly lower. The lowest ratio of functional CMV-specific T cells was found in an IRP individual. A thorough longitudinal analysis of the CMV-specific T cells in nonagenarians showed a stable pattern with respect to frequency, phenotype, and clonal composition. We hypothesize that the number of different CD8 T cell clonal expansions increases as the individual ages, possibly, as a compensatory mechanism to control latent infections, e.g., CMV, but eventually a point is reached where clonal exhaustion leads to shrinkage of the CD8 clonal repertoire, associated with decreased survival.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Infecções por Citomegalovirus / Linfócitos T CD8-Positivos / Citomegalovirus Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Aged80 / Female / Humans / Male Idioma: En Revista: J Immunol Ano de publicação: 2006 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Infecções por Citomegalovirus / Linfócitos T CD8-Positivos / Citomegalovirus Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Aged80 / Female / Humans / Male Idioma: En Revista: J Immunol Ano de publicação: 2006 Tipo de documento: Article