| Project/Area Number |
18390380
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
TOMITA Yukihiro Kyushu University, Department of Cardiovascular Surgery, Faculty of Medicine, Associate Professor (90180174)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAI Yasunobu Kyushu University, Research Center for Prevention of Infectious Diseases, Medical Institute of Bioregulation, Professor (90158402)
TANOUE Yoshihisa KYUSHU UNIVERSITY, Department of Cardiovascular Surgery Faculty of Medicine, Assistant Professor (40372742)
梶原 隆 九州大学, 大学病院, 医員 (30403942)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,510,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2007: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2006: ¥8,800,000 (Direct Cost: ¥8,800,000)
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| Keywords | tolerance / cyclophosphamide / NKT cell / NKT KO mouse / chimerism / cyclophosphamide / cyclophosphamlde / NKT KOマウス |
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| Research Abstract |
Cyclophosphamide (CP) -induced tolerance is a mixed chimerism-based tolerance induction protocol. Recently, we reported that invariant natural killer T (iNKT) cells were essential for the tolerance induction in this system. In this study we evaluated the roles of the cytokines produced by iNKT cells. DBA/2 (H-2^d) mice and BALB/c(H-2^d)wild-type (WT) or iNKT knockout (KO) mice were used as donors and recipients. WT recipients received three doses(days -7. -4, -1 or 35, 38, 41)or a single dose (day -1 or 0) of a-galactosylceramide (GC) in conjunction with our conditioning regimen, which consisted of 10^8 donor spleen cells (SC) on day 0 and 200 mg/kg CP on day 2. To investigate the iNKT cell function, iNKT KO recipients were reconstituted with cytokine(IFN-y. IL-4,or IL-10)KO iNKT cells and received donor SC and CP.
Mixed chimerism was observed in WT recipients, but was reduced in iNKT KO recipients. However, mixed chimerism was absent in WT recipients given GC on days -7, -4, -1, but not in WT recipients given GC on day 35, 38, 41. Donor skin grafts were chronically rejected when mixed chimerism was diminished. Skin grafts were accepted in iNKT KO recipients reconstituted with iNKT cells from IFN-y, IL-4, or IL-10 KO mice and receiving our conditioning regimen. iNKT cells were required in the initial phase of the induction of chimerism. Our results indicated that known major cytokines produced by iNKT cells were dispensable for the regulatory function of iNKT cells.
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