Cargando…

Gene expression changes in long-term culture of T-cell clones: genomic effects of chronic antigenic stress in aging and immunosenescence

The adaptive immune response requires waves of T-cell clonal expansion on contact with altered self and contraction after elimination of antigen. In the case of persisting antigen, as occurs for example in cytomegalovirus or Epstein–Barr virus infection, this critical process can become dysregulated...

Descripción completa

Detalles Bibliográficos
Autores principales: Mazzatti, Dawn J, White, Andrew, Forsey, Rosalyn J, Powell, Jonathan R, Pawelec, Graham
Formato: Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2049045/
https://www.ncbi.nlm.nih.gov/pubmed/17286612
http://dx.doi.org/10.1111/j.1474-9726.2007.00269.x
_version_ 1782137175245062144
author Mazzatti, Dawn J
White, Andrew
Forsey, Rosalyn J
Powell, Jonathan R
Pawelec, Graham
author_facet Mazzatti, Dawn J
White, Andrew
Forsey, Rosalyn J
Powell, Jonathan R
Pawelec, Graham
author_sort Mazzatti, Dawn J
collection PubMed
description The adaptive immune response requires waves of T-cell clonal expansion on contact with altered self and contraction after elimination of antigen. In the case of persisting antigen, as occurs for example in cytomegalovirus or Epstein–Barr virus infection, this critical process can become dysregulated and responding T-cells enter into a dysfunctional senescent state. Longitudinal studies suggest that the presence of increased numbers of such T-cells is a poor prognostic factor for survival in the very elderly. Understanding the nature of the defects in these T-cells might facilitate intervention to improve immunity in the elderly. The process of clonal expansion under chronic antigenic stress can be modelled in vitro using continuously cultured T-cells. Here, we have used cDNA array technology to investigate differences in gene expression in a set of five different T-cell clones at early, middle and late passage in culture. Differentially expressed genes were confirmed by real-time polymerase chain reaction, and relationships between these assessed using Ingenuity Systems evidence-based association analysis. Several genes and chemokines related to induction of apoptosis and signal transduction pathways regulated by transforming growth factor β (TGFβ), epidermal growth factor (EGF), fos and β-catenin were altered in late compared to early passage cells. These pathways and affected genes may play a significant role in driving the cellular senescent phenotype and warrant further investigation as potential biomarkers of aging and senescence. These genes may additionally provide targets for intervention.
format Text
id pubmed-2049045
institution National Center for Biotechnology Information
language English
publishDate 2007
publisher Blackwell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-20490452007-11-02 Gene expression changes in long-term culture of T-cell clones: genomic effects of chronic antigenic stress in aging and immunosenescence Mazzatti, Dawn J White, Andrew Forsey, Rosalyn J Powell, Jonathan R Pawelec, Graham Aging Cell Original Articles The adaptive immune response requires waves of T-cell clonal expansion on contact with altered self and contraction after elimination of antigen. In the case of persisting antigen, as occurs for example in cytomegalovirus or Epstein–Barr virus infection, this critical process can become dysregulated and responding T-cells enter into a dysfunctional senescent state. Longitudinal studies suggest that the presence of increased numbers of such T-cells is a poor prognostic factor for survival in the very elderly. Understanding the nature of the defects in these T-cells might facilitate intervention to improve immunity in the elderly. The process of clonal expansion under chronic antigenic stress can be modelled in vitro using continuously cultured T-cells. Here, we have used cDNA array technology to investigate differences in gene expression in a set of five different T-cell clones at early, middle and late passage in culture. Differentially expressed genes were confirmed by real-time polymerase chain reaction, and relationships between these assessed using Ingenuity Systems evidence-based association analysis. Several genes and chemokines related to induction of apoptosis and signal transduction pathways regulated by transforming growth factor β (TGFβ), epidermal growth factor (EGF), fos and β-catenin were altered in late compared to early passage cells. These pathways and affected genes may play a significant role in driving the cellular senescent phenotype and warrant further investigation as potential biomarkers of aging and senescence. These genes may additionally provide targets for intervention. Blackwell Publishing Ltd 2007-04-01 /pmc/articles/PMC2049045/ /pubmed/17286612 http://dx.doi.org/10.1111/j.1474-9726.2007.00269.x Text en © 2007 The Authors Journal compilation © Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 2007 https://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Original Articles
Mazzatti, Dawn J
White, Andrew
Forsey, Rosalyn J
Powell, Jonathan R
Pawelec, Graham
Gene expression changes in long-term culture of T-cell clones: genomic effects of chronic antigenic stress in aging and immunosenescence
title Gene expression changes in long-term culture of T-cell clones: genomic effects of chronic antigenic stress in aging and immunosenescence
title_full Gene expression changes in long-term culture of T-cell clones: genomic effects of chronic antigenic stress in aging and immunosenescence
title_fullStr Gene expression changes in long-term culture of T-cell clones: genomic effects of chronic antigenic stress in aging and immunosenescence
title_full_unstemmed Gene expression changes in long-term culture of T-cell clones: genomic effects of chronic antigenic stress in aging and immunosenescence
title_short Gene expression changes in long-term culture of T-cell clones: genomic effects of chronic antigenic stress in aging and immunosenescence
title_sort gene expression changes in long-term culture of t-cell clones: genomic effects of chronic antigenic stress in aging and immunosenescence
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2049045/
https://www.ncbi.nlm.nih.gov/pubmed/17286612
http://dx.doi.org/10.1111/j.1474-9726.2007.00269.x
work_keys_str_mv AT mazzattidawnj geneexpressionchangesinlongtermcultureoftcellclonesgenomiceffectsofchronicantigenicstressinagingandimmunosenescence
AT whiteandrew geneexpressionchangesinlongtermcultureoftcellclonesgenomiceffectsofchronicantigenicstressinagingandimmunosenescence
AT forseyrosalynj geneexpressionchangesinlongtermcultureoftcellclonesgenomiceffectsofchronicantigenicstressinagingandimmunosenescence
AT powelljonathanr geneexpressionchangesinlongtermcultureoftcellclonesgenomiceffectsofchronicantigenicstressinagingandimmunosenescence
AT pawelecgraham geneexpressionchangesinlongtermcultureoftcellclonesgenomiceffectsofchronicantigenicstressinagingandimmunosenescence