The SPECIFIC AIMS in non-human primate kidney transplant model are to: 1) determine whether short-term costimulation blockade based therapy, a treatment that is not directly lympholytic, can be made more effective through use of concomitant treatment with drugs that enhance T-cell activation induced cell death (AICD), e.g. rapamycin or methotrexate (MTX). 2) determine short-term costimulation blockade based therapy, a treatment that is not directly lympholytic, can be made more effective through use of concomitant treatment with a cytoreductive anti-CD8 mAb. 3) determine whether short-term costimulation blockade based therapy can be made more effective through use of concomitant treatment with an Ig-related fusion protein (mutant IL-15/Fc) that blocks and temporarily destroys the IL-15/IL-15R network. 4) identify the time-related pattern of donor reactive T-cell frequency as well as cellular and molecular events that are involved in the acquisition and maintenance of allograft tolerance. 5) determine whether organ transplant recipients, who are withdrawn from a potentially tolerizing therapy can be monitored for incipient graft rejection so that, when needed, appropriate immunosuppressive therapy can be instituted before irreversible rejection takes place. 6) determine whether an idealized therapeutic and diagnostic protocol can be established through knowledge gained from the combined efforts of each of the components of this project.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI050987-04
Application #
6756408
Study Section
Special Emphasis Panel (ZAI1-NBS-I (S1))
Program Officer
Kraemer, Kristy A
Project Start
2001-09-30
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
4
Fiscal Year
2004
Total Cost
$656,799
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Koulmanda, M; Sampathkumar, R S; Bhasin, M et al. (2014) Prevention of nonimmunologic loss of transplanted islets in monkeys. Am J Transplant 14:1543-51
Moraes-Vieira, P M M; Bassi, E J; Larocca, R A et al. (2013) Leptin modulates allograft survival by favoring a Th2 and a regulatory immune profile. Am J Transplant 13:36-44
Yamada, Y; Boskovic, S; Aoyama, A et al. (2012) Overcoming memory T-cell responses for induction of delayed tolerance in nonhuman primates. Am J Transplant 12:330-40
Koulmanda, Maria; Bhasin, Manoj; Fan, Zhigang et al. (2012) Alpha 1-antitrypsin reduces inflammation and enhances mouse pancreatic islet transplant survival. Proc Natl Acad Sci U S A 109:15443-8
Aoyama, A; Klarin, D; Yamada, Y et al. (2012) Low-dose IL-2 for In vivo expansion of CD4+ and CD8+ regulatory T cells in nonhuman primates. Am J Transplant 12:2532-7
Nadazdin, Ognjenka; Abrahamian, Gregory; Boskovic, Svjetlan et al. (2011) Stem cell mobilization and collection for induction of mixed chimerism and renal allograft tolerance in cynomolgus monkeys. J Surg Res 168:294-300
Koyama, I; Nadazdin, O; Boskovic, S et al. (2007) Depletion of CD8 memory T cells for induction of tolerance of a previously transplanted kidney allograft. Am J Transplant 7:1055-61
Koulmanda, M; Smith, R N; Qipo, A et al. (2006) Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term anti-CD154-based therapy: nonimmunologic graft failure? Am J Transplant 6:687-96
Boskovic, Svjetlan; Kawai, Tatsuo; Smith, Rex-Neal et al. (2006) Monitoring antidonor alloantibodies as a predictive assay for renal allograft tolerance/long-term observations in nonhuman primates. Transplantation 82:819-25
Kawai, Tatsuo; Sogawa, Hiroshi; Boskovic, Svetlan et al. (2004) CD154 blockade for induction of mixed chimerism and prolonged renal allograft survival in nonhuman primates. Am J Transplant 4:1391-8

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