The Immunopathology Core is a central resource for all three projects in the PPG.
The Specific Aims are to provide: 1) expert pathological and immunopathological interpretation of the allograft in each of the three projects, which is critical in the evaluation of tolerance or rejection; 2) innovative staining methods directed at answering the specific scientific questions that arise in each of the projects as requested by the investigators; 3) high quality, uniform histochemical/immunohistochemical preparations common to all projects. 4) advice on the design of experiments to optimize the potential pathological studies; 5) ready investigator access to scanned images and digital photographs for publication; and 6) common and advanced computer analysis for morphometrics and 3-D reconstruction. Each project will use the Core to determine the status of the allograft along the axis of tolerance--rejection, and the specific features of either (e.g., are there intragraft Treg-rich organized lymphoid structures (TOLS) or is the graft free of infiltrate; is the rejection antibody or T cell mediated?). The techniques to be provided include: standard scoring of allograft samples (Banff, ISHLT and custom schema), immunohistochemistry and immunofluorescence for cell identification and status, whole slide digital imaging and morphometrics for quantitation of infiltrates and vascular lesions. Each project will use the Core to determine the status of the allograft along the axis of tolerance--rejection, and the specific intragraft features of either. The results from the Core analysis will be essential to assess the success and mechanisms of the protocols.

Public Health Relevance

The goal of the PPG is to discover and evaluate the mechanisms by which kidney allografts induce tolerance to the heart. The expertise and techniques of the Immunopathology Core are essential to determine the end- point, graft tolerance or rejection, and to give insights into potential mechanisms by which tolerance is achieved.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI123086-05
Application #
9987471
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2016-08-05
Project End
2021-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
Hotta, Kiyohiko; Oura, Tetsu; Dehnadi, Abbas et al. (2018) Long-term Nonhuman Primate Renal Allograft Survival Without Ongoing Immunosuppression in Recipients of Delayed Donor Bone Marrow Transplantation. Transplantation 102:e128-e136
Robinson, Kortney A; Orent, William; Madsen, Joren C et al. (2018) Maintaining T cell tolerance of alloantigens: Lessons from animal studies. Am J Transplant 18:1843-1856
Sasaki, Hajime; Oura, Tetsu; Spitzer, Thomas R et al. (2018) Preclinical and clinical studies for transplant tolerance via the mixed chimerism approach. Hum Immunol 79:258-265
Michel, S G; Madariaga, M L L; LaMuraglia 2nd, G M et al. (2018) The effects of brain death and ischemia on tolerance induction are organ-specific. Am J Transplant 18:1262-1269
Smith, R N; Adam, B A; Rosales, I A et al. (2018) RNA expression profiling of renal allografts in a nonhuman primate identifies variation in NK and endothelial gene expression. Am J Transplant 18:1340-1350
Chatterjee, Debanjana; Moore, Carolina; Gao, Baoshan et al. (2018) Prevalence of polyreactive innate clones among graft--infiltrating B cells in human cardiac allograft vasculopathy. J Heart Lung Transplant 37:385-393
Smith, R N; Matsunami, M; Adam, B A et al. (2018) RNA expression profiling of nonhuman primate renal allograft rejection identifies tolerance. Am J Transplant 18:1328-1339
Wang, Zhaohui; Louras, Nathan J; Lellouch, Alexandre G et al. (2018) Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4+ Treg in nonhuman primates. Mol Oncol 12:1374-1382
Madsen, Joren C (2017) Advances in the immunology of heart transplantation. J Heart Lung Transplant 36:1299-1305
Alessandrini, Alessandro; Turka, Laurence A (2017) FOXP3-Positive Regulatory T Cells and Kidney Allograft Tolerance. Am J Kidney Dis 69:667-674

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