1995 Fiscal Year Final Research Report Summary
Prolonged rat hepatic allograft survival by intrathymic administration of donor antigens : the role of antigen presenting cells (dendritic cells) and Th2 cells
| Project/Area Number |
06807099
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
General surgery
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
YAMAGUCHI Yasuo Department of Surgery II,Instructor Kumamoto University, 医学部, 助手 (90253757)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MORI Katsutaka College of Medical Science, Professor Kumamoto University, 医療技術短期大学部, 教授 (10040213)
OGAWA Michio Department of Surgery II,Professor Kumamoto University, 医学部, 教授 (30028691)
|
|---|
| Project Period (FY) |
1994 – 1995
|
| Keywords | Immunologic tolerance / Liver transplantation / Rejection / Thymus / Th2 cells / CD4 cells / CD8 cells / OX22 (CD45RC) |
|---|
| Research Abstract |
The present sudy was undertaken to investigate the roles of antigen presenting cells (dendritic cells) and Th2 cell for immunologic unresponsiveness induced by preoperative administration of donor antigens in rat hepatic allografts.
1).FACS analysis revealed that there were two phenotypes of CD4^+ T cells infiltrated in hepatic allografts, CD45RC^-CD4^+ T and CD45RC^+CD4^+ T cells. RT-PCR demonstrated that CD45RC^-CD4^+ T expressed IL-4 and IL-10 mRNA,suggesting these cells may be Th2-like effector cells.
2).The discrimination of Th1 and Th2 cells, which used to be determined by secretory cytokine patterns, could be made by the expression of leukocyte common antigen (CD45RC) on the cell surface.
3).CD45RC^-CD4^+ T cells dominantly distributed in prolonging hepatic allografts pretreated with donor antigens. However, these cells were seen in neither spleen nor lymph nodes.
4).Plasma levels of hepatocyte growth factor (HGF) in the recipients of hepatic allografts pretreated with donor antigen
… More
s were significantly higher than those in untreated allograft recipients.
5).Immunostaining revealed that HGF^+ cells mainy distributed in the portal areas of hepatic allografts pretreated with donor antigens. HGF^+ cells were also observed in the red pulp of the recipient spleen.
6).Double immunostainig demonstrated the phenotypes of HGF^+ cells, HGF^+ED1^+ and HGF^+ED2^+ cells.
7).We investigated the implication of increased plasma levels of HGF in prolonging hepatic allografts accumlated mainly by Th2-like effector cells. HGF enhanced the migration of Th2 cells in vitro.
8).FACS analysis revealed two phenotypes of CD8^+ T cells infiltrated in hepatic allografts, CD45RC^-CD8^+ and CD45RC^+CD8^+ T cells.
9).CD45RC^-CD8^+ T cells significantly increased in hepatic allografts pretreated with donor antigens than untreated allografts. CD45RC^-CD8^+ T cells expressed IL-4 and IL-10 mRNA,suggesting that these cells may be Th2 type cells
In summary, CD45RC^-CD4^+ T and CD45RC^-CD8^+ T cells significantly increased in prolonging hepatic allografts pretreated with donor antigens. This may be one of the mechanisms underlying immunologic unresponsiveness induced by pretreatment with donor anrigens. Less
|
