Core A will perform all pathology tissue studies in this program project. The Core will be led by Robert B. Colvin, M.D., who is the Benjamin Castleman Distinguished Professor of Pathology at Harvard/Massachusetts General Hospital. He is an internationally recognized investigator in transplantation pathology and has collaborated extensively in the past with the other investigators. He will be joined in this effort by R. Neal Smith, Associate Professor of Pathology, who has expertise in islet transplantation pathology and Sandro Alessandrini, Assistant Professor of Surgery (Immunology), who has experience with endothelial activation pathways, Treg and dendritic cells. The studies will be performed in the Immunopathology Research Laboratory at the Massachusetts General Hospital (Thier 8). No embryonic stem cells will be used. The techniques that will be utilized include routine histology, immunohistochemistry, immunofluorescence, and electron microscopy. Immunoperoxidase techniques with a panel of mAbs will distinguish the infiltrating cell types (Teff, Treg, Breg, et al), adhesion and cytokine molecules and receptors, complement deposition (C4d), and endothelial activation markers (e.g., pERK). Analysis ofthe in situ processes will be enhanced by whole slide digital scans and morphometry. The pathology results will be correlated with functional and molecular studies done in the projects. In addition, complete necropsies will be done on all animals, with samples from all major organs analyzed by routine and special techniques as indicated.

Public Health Relevance

The pathology studies in Core A are essential to evaluate the status of the allografts and the effects of the intervention to reduce inflammation and parenchymal injury. The studies are critical to determine the nature and location of the cells infiltrating the graft, the role of antibodies in rejection and systemic toxicity of treatment. The primary role is to document and characterize: 1) The status of the kidney and islet grafts (nature of infiltrate, presence of acute or chronic rejection, including a humoral component;quantitation of lesions, presence of transplanted islet cells in liver of beneath the kidney capsule 2) Systemic effects ofthe protocols (toxicity, complications, BK viral infection, PTLD) 3) Intragraft markers that predict acceptance vs. rejection 4) Mechanisms by which intragraft cells may promote rejection or acceptance

National Institute of Health (NIH)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Peraino, Jaclyn Stromp; Zhang, Huiping; Rajasekera, Priyani V et al. (2014) Diphtheria toxin-based bivalent human IL-2 fusion toxin with improved efficacy for targeting human CD25(+) cells. J Immunol Methods 405:57-66
Yamada, Y; Ochiai, T; Boskovic, S et al. (2014) Use of CTLA4Ig for induction of mixed chimerism and renal allograft tolerance in nonhuman primates. Am J Transplant 14:2704-12
Scalea, Joseph R; Villani, Vincenzo; Gillon, Bradford C et al. (2014) Development of antidonor antibody directed toward non-major histocompatibility complex antigens in tolerant animals. Transplantation 98:514-9
Scalea, Joseph R; Torabi, Radbeh; Tena, Aseda et al. (2014) The rejuvenating effects of leuprolide acetate on the aged baboon's thymus. Transpl Immunol 31:134-9
Kawai, Tatsuo; Sachs, David H; Sykes, Megan et al. (2013) HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 368:1850-2
Kawai, Tatsuo; Sachs, David H (2013) Tolerance induction: hematopoietic chimerism. Curr Opin Organ Transplant 18:402-7