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Altered CD45 expression in C77G carriers influences immune function and outcome of hepatitis C infection

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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