1998 Fiscal Year Final Research Report Summary
Mechanism of allograft rejection : molecular biological analysis of delf/nonself recognition
| Project/Area Number |
09680636
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Osaka Medical College |
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Principal Investigator |
YOSHIDA Ryotaro Osaka Medical College Physiology, Associate Professor, 医学部, 助教授 (10124760)
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| Project Period (FY) |
1997 – 1998
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| Keywords | self / nonself / cytotoxic T cells / macrophages / apoptosis / Fas / FasL / perforin / histocompatibility antigen / skin allograft rejection |
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| Research Abstract |
When BALB/c skin or Meth A fibrosarcoma cells (BALB/c origin) was transplanted to C57BL/6 mice, two types of cytotoxic cells [i.e., CD8^+ cytotoxic T lymphocytes (CTLs) and macrophages (Mphis)] infiltrated into the rejection site. The Mphis lysed the allografted skin components or the tumor cells but were inert toward donor-type lymphoblasts. By contrast, the CTLs were inactive against the allografts, whereas they were cytotoxic against the donor-reated lymphoblasts. The infiltration of Mphis preceded the infiltration of CTLs by several days during the course of rejection. As nobody has expected that there were two types of cytotoxic cells infiltrating into the rejection site, most of the previous investigators have concluded that T lymphocytes are the effector cells.
The allograft-induced Mphis induced the apoptotic death of allografted cells through a third mechanism, one other than the Fsa/FasL- and perform-based pathways and the mice rejected the allografi on days 9-11 after transplantation. The Mphi population in bulk infiltrates from the rejection site was cytotoxic against allografted, but not self, skin components even in the absence of T cells. In addition, the Mphi-mediated cytotoxicity against the allograft was antibody-independent. Therefore, we prepared a cDNA library from allograft-induced Mphis and established several clones of monoclonal antibodies to the Mphis.
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