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Features of immune senescence in liver transplant recipients with established grafts†‡

  1. William Gelson1,
  2. Matthew Hoare1,
  3. Sarah Vowler2,
  4. Arun Shankar1,
  5. Paul Gibbs3,
  6. Arne N. Akbar4,
  7. Graeme J. M. Alexander1,§,*

Article first published online: 25 JAN 2010

DOI: 10.1002/lt.22033

Issue

Liver Transplantation

Liver Transplantation

Volume 16, Issue 5, pages 577–587, May 2010

Additional Information

How to Cite

Gelson, W., Hoare, M., Vowler, S., Shankar, A., Gibbs, P., Akbar, A. N. and Alexander, G. J. M. (2010), Features of immune senescence in liver transplant recipients with established grafts. Liver Transpl, 16: 577–587. doi: 10.1002/lt.22033

Author Information

  1. 1

    Department of Medicine, University of Cambridge, Cambridge, UK

  2. 2

    Centre for Applied Medical Statistics, University of Cambridge, Cambridge, UK

  3. 3

    Department of Surgery, University of Cambridge, Cambridge, UK

  4. 4

    Department of Immunology, University College London, London, UK

  1. §

    Telephone: 01223 586614; FAX: 01223 216111

*Department of Medicine (Box 157), Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB0 2QQ, United Kingdom

  1. †

    The British Transplantation Society supported Dr. William Gelson; The Wellcome Trust supported Dr. Matthew Hoare. The Frank Litchfield Charitable Trust and Cambridge Hepatology Endowment Fund provided financial support for the running costs of the study.

  2. ‡

    See Editorial on Page 548

  3. §

    Telephone: 01223 586614; FAX: 01223 216111

Publication History

  1. Issue published online: 28 APR 2010
  2. Article first published online: 25 JAN 2010
  3. Accepted manuscript online: 25 JAN 2010 12:00AM EST
  4. Manuscript Accepted: 16 JAN 2010
  5. Manuscript Received: 14 NOV 2009

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Abstract

Immune senescence is the normal process whereby the human immune system ages, but becomes less effective. We investigated whether liver transplant recipients have features of immune senescence. Lymphocytes from 97 liver transplant recipients with established grafts and 41 age-matched and sex-matched controls were subjected to an 8-color flow cytometry assay that measured expression of killer cell lectin-like receptor subfamily G member 1, cluster of differentiation 127 (CD127), CD45RO, CD27, CD28, CD4, CD8, and CD57. Lymphocyte telomere length was assessed by flow-fluorescence in situ hybridization. Cases were compared with controls for each marker of immune senescence using a Mann-Whitney U test. For liver transplant recipients, linear regression analyses identified associations between markers of immune senescence and clinical or demographic characteristics. Lymphocytes from liver transplant recipients expressed more phenotypic markers of maturity than did lymphocytes from controls. Lymphocyte telomeres were shorter in liver transplant recipients than in controls. Age, hepatocellular carcinoma at transplantation, and skin malignancy developing after transplantation were associated independently with shortened lymphocyte telomeres. Increasing age and previous cytomegalovirus infection were associated independently with phenotypic markers of lymphocyte maturity. Thus, lymphocytes from liver transplant recipients are older “biologically” than lymphocytes from age-matched and sex-matched controls. Hepatocellular carcinoma at transplantation, subsequent skin malignancy, and previous cytomegalovirus infection are associated with lymphocyte senescence in liver transplant recipients. Liver Transpl 16:577-587, 2010. © 2010 AASLD.

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