2007 Fiscal Year Final Research Report Summary
Role of the Cytokine Profiles Produced by iNKT Cells in the Initial Phase of Cyclophosphamide-Induced Tolerance^1
| Project/Area Number |
18390380
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Thoracic surgery
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
TOMITA Yukihiro Kyushu University, Department of Cardiovascular Surgery, Faculty of Medicine, Associate Professor (90180174)
|
|---|
| 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)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Keywords | tolerance / cyclophosphamide / NKT cell / NKT KO mouse / chimerism |
|---|
| 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.
|
-
[Journal Article] Application of Cyclophsphamide-induced Tolerance in al,3-galactosyltransferase Knockout Mice Presensitized with Galal-3Galβ-4-GlcNAc Antigens.2008
Author(s)
Tatsushi, Onzuka, Ichiro, Shimizu, Yukihiro, Tomita, Toshiro, Iwai, Shinji, Okano, Ryuji, Tominaga
-
Journal Title
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
[Journal Article] The Immunoregulatory Roles of Natural Killer T Cells in Cyclophosphamide-Induced Tolerance.2007
Author(s)
Iwai, T., Y., Tomita, I., Shimizu, T., Kajiwara, T., Onzuka, S., Okano, Y., Yasunami, Y., Yoshikai, K., Nomoto, R., Tominaga
-
Journal Title
Transplantation 84
Pages: 1686-1695
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Influence of the Th1/Th2 paradigm for the regulatory function of the natural killer T (NKT) cells in cyclophosphamide (CP)-induced tolerance.2007
Author(s)
Tatsushi, Onzuka, Ichiro, Shimizu, Yukihiro, Tomita, Toshiro, Iwai, Shinji, Okano, Ryuji, Tominaga
-
Journal Title
American Journal of Transplantation(Supp.) 7
Pages: 485
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
[Presentation] Influence of the Th1/Th2 paradigm for the regulatory function of the natural killer T(NKT) cells in cyclophosphamide(CP) -induced tolerance.2007
Author(s)
Tatsushi, Onzuka, Ichiro, Shimizu, Yukihiro, Tomita, Toshiro, Iwai, Shinji, Okano, Ryuji, Tominaga
Organizer
American Transplant Congress
Place of Presentation
San Francisco
Year and Date
2007-05-07
Description
「研究成果報告書概要(欧文)」より
