| Co-Investigator(Kenkyū-buntansha) |
MIYAZAWA Yukihisa Teikyo University, School of Medicine, Professor, 医学部, 教授 (60143442)
IKEDA Yoshifumi Teikyo University, School of Medicine, Associated Prof, 医学部, 助教授 (20222870)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Background: We previously reported that intratracheal delivery (ITD) of alloantigen generated regulatory cells in mice. Here, we examined the effect of various doses of conventional immunosuppressants (FK506, cyclosporine, azathioprine, mycophenolate mofetil (MMF), and rapamycin) on inducing regulatory cells in our model.
Methods: CBA mice (primary recipients) were given C57BL/6 splenocytes by ITD and either no additional treatment or various doses of an immunosuppressant. Seven days later, splenocytes from these mice were adoptively transferred into naive secondary CBA recipients that underwent C57BL/6 cardiac grafting the same day.
Results: Adoptive transfer from primary recipients given ITD of splenocytes alone induced prolonged allograft survival in secondary recipients (median survival time (MST), 50 days), suggesting that regulatory cells were generated. When ITD of alloantigen was combined with daily administration of 0.1 mg/kg FK506 or 0.2 mg/kg rapamycin, graft survival was similarly prolonged (MST, 55, 50 days, respectively). When combined with 20 or 40 mg/kg MMF or 0.4 mg/kg rapamycin, the majority of recipients had indefinite survival (MST, 100< days in all groups). When ITD of alloantigen was combined with 0.3, 0.5, or 1.0 mg/kg FK506; 5, 10, or 25 mg/kg cyclosporine; or 1.0 or 2.0 mg/kg azathioprine, allografts were rejected acutely (MST, ranged from 7 to 13 days).
Conclusion: Generation of regulatory cells by ITD of alloantigen was facilitated by MMF and high doses of rapamycin but abrogated by cyclosporine, azathioprine, and high doses of FK506. Low doses of rapamycin and of FK506 did not interfere with generation of regulatory cells.
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