Altered CD45 expression in C77G carriers influences immune function and outcome of hepatitis C infection.
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.
Dawes
R
R
Hennig
B
B
Irving
W
W
Petrova
S
S
Boxall
S
S
Ward
V
V
Wallace
D
D
Macallan
D C
DC
Thursz
M
M
Hill
A
A
Bodmer
W
W
Beverley
P C L
PC
Tchilian
E Z
EZ
D000818:Animals; D015415:Biomarkers; D002353:Carrier State / Q000276:immunology*; D049109:Cell Proliferation; D005091:Exons / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006526:Hepatitis C / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000235:genetics* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D015415:Biomarkers; D017493:Leukocyte Common Antigens