The 33rd Annual Congress of The Japan Society for TransplantationRole of Regulatory T Cells in the “Infectious” Tolerance Pathway in Transplant Recipients☆
Section snippets
Allograft Model
Lewis (RT1l) rats were sensitized with Brown Norway (RT1n) skin grafts (day −7), followed 1 week later (day 0) by transplantation of LBNF1 hearts. These cardiac allografts are rejected inevitably in an accelerated manner in less than 36 hours (acute rejection occurs at 7 to 8 days).1, 2RIB-5/2 mAb, a mouse antirat nondepleting CD4 mAb (IgG2a), was administered to experimental animals (20 mg/kg/per day IV) at days −7, −4, −1, 0, 1, 4, 7, 10, 14, and 21.
Flow Microfluorimetry Analysis
Peripheral blood leukocytes (PBL), as well
Results
Treatment with RIB-5/2 mAb (day −7 to +21) uniformly produced permanent acceptance of cardiac allografts in presensitized rat recipients except for two graft rejections. This CD4-targeted therapy was generally well tolerated, and of 65 treated rats only three (less than 5%) died between day 70 and 200 posttransplant. Postmortem examination revealed no signs of allograft rejection. No side effects were noted in any of the remaining (N = 60) long-term transplant recipients.
Cell surface phenotype
Discussion
The results of this study extend our previous findings,1, 2and add to our better understanding of the complex immune mechanisms contributing to the “infectious” tolerance pathway in transplant recipients. The exceptional efficacy of the CD4 nondepleting regimen to induce transplantation tolerance in this stringent accelerated-rejection cardiac allograft model is accompanied by a relatively low mortality rate and no side effects in long-term hosts. The early depression of CD4+ cells at the
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Cell therapy with autologous tolerogenic dendritic cells induces allograft tolerance through interferon-gamma and Epstein-Barr virus-induced gene 3
2011, American Journal of TransplantationFunctional compartmentalization following induction of long-term graft survival with pregraft donor-specific transfusion
2007, American Journal of TransplantationTh1 cytokines, programmed cell death, and alloreactive T cell clone size in transplant tolerance
2002, Journal of Clinical Investigation
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This work was supported by USPHS grant AI23847 and AI34965.