Analysis of intragraft gene and protein expression of the costimulatory molecules, CD80, CD86 and CD154, in orthotopic liver transplant recipients.
CD40-CD154 and/or CD28-CD80/86 costimulatory blockade induces long-term allograft survival in numerous animal models. Studies examining the expression of costimulatory molecules during acute cellular rejection (ACR) have been limited to renal and cardiac allografts. The aim of this study was to describe the relationship between intragraft costimulatory molecule expression in OLT recipients and ACR. Forty-five liver biopsies were obtained at reperfusion and day 7. Gene and protein expression of CD80, CD86 and CD154 were analyzed by RT-PCR and immunohistochemistry. CD154 protein expression was present in 13 of 18 patients with a RAI score of 4, but in only two of 14 patients with a RAI score of <4. There was a strong association between the RAI score and the presence of CD80 and CD154 immunoreactivity. CD86 protein expression did not correlate with the severity of ACR. In reperfusion biopsies CD154, but not CD80 or CD86, protein expression correlated with the total ischaemic time. There was no association between expression of costimulatory molecule genes and ACR. In conclusion, we have demonstrated an association between CD154 and CD80 protein expression and ACR in orthotopic liver allografts.
Bartlett
Adam S R
AS
Division of Surgery, University of Auckland, Auckland, New Zealand.
McCall
John L
JL
Ameratunga
Rohan
R
Yeong
Mee-Ling
ML
Gane
Ed
E
Munn
Stephen R
SR
D015703:Antigens, CD / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D001706:Biopsy; D023201:CD40 Ligand / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D016031:Liver Transplantation / Q000379:methods*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D015427:Reperfusion Injury; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D023201:CD40 Ligand