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Altered CD45 expression in C77G carriers influences immune function and outcome of hepatitis C infection
  1. R Dawes1,
  2. B Hennig2,
  3. W Irving3,
  4. S Petrova4,
  5. S Boxall4,
  6. V Ward5,
  7. D Wallace6,
  8. D C Macallan7,
  9. M Thursz8,
  10. A Hill9,
  11. W Bodmer10,
  12. P C L Beverley11,
  13. E Z Tchilian11
  1. 1Edward Jenner Institute for Vaccine Research, Compton, Berkshire, UK
  2. 2Wellcome Trust Centre for Human Genetics, Headington, Oxford, UK
  3. 3Division of Microbiology and Infectious Diseases, Queen’s Medical Centre, University of Nottingham, Nottingham, UK
  4. 4Edward Jenner Institute for Vaccine Research, Compton
  5. 5Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, Cancer Research UK, John Radcliffe Hospital, Oxford
  6. 6Edward Jenner Institute for Vaccine Research, Compton
  7. 7Centre of Infection, St George’s Hospital, University of London, London SW17, UK
  8. 8Hepatology Division, Imperial College Faculty of Medicine, St Mary’s Hospital, London W2, UK
  9. 9Wellcome Trust Centre for Human Genetics, Oxford
  10. 10Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, Oxford
  11. 11Edward Jenner Institute for Vaccine Research, Compton
  1. Correspondence to:
 Dr Elma Tchilian
 The Edward Jenner Institute for Vaccine Research, Compton, Berkshire RG20 7NN, UK; elma.tchilian{at}jenner.ac.uk

Abstract

Background: A polymorphism in exon 4 (C77G) of CD45 that alters CD45 splicing has been associated with autoimmune and infectious diseases in humans.

Objective: To investigate the effect of C77G in hepatitis C virus (HCV) infected individuals and study the phenotype and function of peripheral blood mononuclear cells (PBMC) from healthy and hepatitis C infected C77G carriers.

Results: C77G individuals showed an increased proportion of primed CD45RA and effector memory CD8 T cells and more rapid activation of the lymphocyte specific protein tyrosine kinase (Lck) following CD3 stimulation. Transgenic mice with CD45 expression mimicking that in human C77G variants had more activated/memory T cells, more rapid proliferative responses, and activation of Lck.

Conclusions: Changes in CD45 isoform expression can alter immune function in human C77G variants and CD45 transgenic mice. The C77G allele may influence the outcome of HCV infection.

  • HCV, hepatitis C virus
  • HENCORE, Hepatitis C European Network for Cooperative Research
  • Lck, lymphocyte specific protein tyrosine kinase
  • PBMC, peripheral blood mononuclear cells
  • SNP, single nucleotide polymorphism
  • TcR, T cell receptor
  • CD45
  • C77G variant
  • hepatitis C
  • immune response

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Footnotes

  • Published Online First 1 March 2006

  • Conflicts of interest: none declared

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