Anti-Inflammatory Approaches

Massachusetts General Hospital, Boston MA

Investigators

Linked publications & trials

Abstract

PROJECT SUMMARY (See instructions): Our recent data show that cynomolgus transplant recipients are resistant to the induction of chimerism and transplant tolerance until the pro-inflammatory state that arises in the peri-transplant period and continues for weeks to months thereafter abates. Projects 1 and 2 place heavy emphasis upon the role of inflammation in influencing the allograft response toward or away from transplant tolerance. In accordance with this logic, Core B will interact with all of the Project 1 and 2 in vivo models, by monitoring and characterizing the state of inflammation and immunity via QRT-PCR in the cynomolgus allograft recipients. Using a panel of custom made reagents crafted for use in cynomolgus monkeys and a powerful pre-amplification technique, we can assess transcription of over 65 genes in a small tissue sample. Going forward we will further develop a single cell PCR method to provide detailed information about the frequency of T cell subsets in recipient blood or tissues. The goal is to favorably tilt the balance of immunity toward allograft protection and tolerance by controlling adverse inflammation. T alpha1 antitrypsin (AAT), an acute phase reactant and serine protease blocker is a potential agent for achieving such balance. It has been given safely as replacement therapy to patients with the AAT gene defect. This protein possesses interesting anti-inflammatory and anti-thrombotic effects. It is a potent islet cytoprotectant and although lacking direct effects upon T cells promotes T cell tolerance. This and other novel agents will be characterized in Core B for use in the Project 1 and 2 models.