Induction of specific immunologic tolerance is an ultimate goal of organ transplantation. Based on the conditioning regimen developed in our laboratory by decades-long research in nonhuman primates (NHP), we have now successfully achieved renal allograft tolerance in HLA mismatched human kidney transplant recipients via the mixed chimerism approach. However, limitations of this approach have been its inapplicability for deceased donor transplantation and the inability to induce tolerance of non-renal organs/cells. To extend this approach to deceased donor transplantation, we recently developed a novel strategy of

Public Health Relevance

Successful induction of allograft tolerance has been achieved in HLA mismatched human kidney transplant recipients via mixed chimerism. This research proposal is directed to identify novel modalities to extend our mixed chimerism approach to a much wider population of human allograft recipients and to islet allograft tolerance. Our NHP model has been proven highly relevant to clinical organ transplantation and observations from these studies should be directly transferrable to clinical application.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI102405-01
Application #
8432084
Study Section
Special Emphasis Panel (ZAI1-MFH-I (M1))
Project Start
2012-08-01
Project End
2017-07-31
Budget Start
2012-08-01
Budget End
2013-06-30
Support Year
1
Fiscal Year
2012
Total Cost
$643,646
Indirect Cost
$246,479
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Oura, T; Hotta, K; Lei, J et al. (2016) Immunosuppression With CD40 Costimulatory Blockade Plus Rapamycin for Simultaneous Islet-Kidney Transplantation in Nonhuman Primates. Am J Transplant :
Oura, Tetsu; Ko, Dicken S C; Boskovic, Svjetlan et al. (2016) Kidney Versus Islet Allograft Survival After Induction of Mixed Chimerism With Combined Donor Bone Marrow Transplantation. Cell Transplant 25:1331-41
Hotta, Kiyohiko; Aoyama, Akihiro; Oura, Tetsu et al. (2016) Induced regulatory T cells in allograft tolerance via transient mixed chimerism. JCI Insight 1:
Kant, Cavit D; Akiyama, Yoshinobu; Tanaka, Katsunori et al. (2015) Both rejection and tolerance of allografts can occur in the absence of secondary lymphoid tissues. J Immunol 194:1364-71
Wang, Ping; Schuetz, Christian; Vallabhajosyula, Prashanth et al. (2015) Monitoring of Allogeneic Islet Grafts in Nonhuman Primates Using MRI. Transplantation 99:1574-81
Tonsho, M; Lee, S; Aoyama, A et al. (2015) Tolerance of Lung Allografts Achieved in Nonhuman Primates via Mixed Hematopoietic Chimerism. Am J Transplant 15:2231-9
Oura, Tetsu; Hotta, Kiyohiko; Cosimi, A B et al. (2015) Transient mixed chimerism for allograft tolerance. Chimerism 6:21-6
Yamada, Y; Nadazdin, O; Boskovic, S et al. (2015) Repeated Injections of IL-2 Break Renal Allograft Tolerance Induced via Mixed Hematopoietic Chimerism in Monkeys. Am J Transplant 15:3055-66
Granados, Jose M M; Benichou, Gilles; Kawai, Tatsuo (2015) Hematopoietic stem cell infusion/transplantation for induction of allograft tolerance. Curr Opin Organ Transplant 20:49-56
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

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