Quantitative mRNA expression analysis of co-stimulatory molecules in sequential biopsies from heart allografts.
Allograft-specific T-cell activation requires two signals, "signal one" via the T-cell receptor and "signal two" via costimulatory pathways. Animal models provide promising data that blockade of costimulatory signals can lead to T-cell anergy and tolerance. We analyzed 72 formalin-fixed and paraffin-embedded sequential heart allograft biopsies from 22 patients by quantitative real-time reverse transcriptase-polymerase chain reaction for the mRNA expression of the costimulatory molecules CD28, CD80, CD86, CD40, and CD154. mRNA expression levels were correlated to histological grade and time-point of rejection. mRNA expression of costimulatory molecules predominantly expressed by antigen-presenting cells (CD80, CD86, CD40), correlated with histological grade of cell-mediated acute rejection. Costimulatory molecules were up-regulated not only during rejection episodes early after transplantation, but also at late occurring rejection. The present results suggest a simultaneous and long-term therapeutical blockade of more than one costimulatory pathway for the prevention of repetitive T-cell mediated acute rejection episodes after heart transplantation.
Akdere
Fatma
F
Institute of Pathology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Bock
Oliver
O
Lehmann
Ulrich
U
Serinsöz
Ebru
E
Haverich
Axel
A
Kreipe
Hans
H
Mengel
Michael
M
D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000378:metabolism; D018122:B7-1 Antigen / Q000096:biosynthesis; D001706:Biopsy; D018106:CD28 Antigens / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand / Q000096:biosynthesis; D017690:Cell Transplantation / Q000379:methods; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005557:Formaldehyde / Q000737:chemistry; D005786:Gene Expression Regulation; D006084:Graft Rejection; D006085:Graft Survival; D016027:Heart Transplantation / Q000379:methods*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010232:Paraffin / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D014184:Transplantation, Homologous / Q000379:methods*
D018122:B7-1 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; D018076:DNA, Complementary; D012333:RNA, Messenger; D023201:CD40 Ligand; D005557:Formaldehyde; D010232:Paraffin