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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.