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Prevention of pulmonary allograft rejection by treatment with antibodies to LFA-1 and ICAM-1.

Research Project

Project/Area Number 04670821
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Thoracic surgery
Research InstitutionNiigata University

Principal Investigator

HIRONO Tatshuhiko  Niigata University School of Medisin 2nd Department of Surgery Assistant Professor, 医学部, 助教授 (60092722)

Co-Investigator(Kenkyū-buntansha) YAMATO Yasusi  Niigata University School of Medicin 2nd Department of Surgery Assistant, 医学部・附属病院, 助手 (40240048)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsPulmonary transplantation / LFA-1 / ICAM-1 / Monoclonal antibody / Rat / 拒絶反応 / ラット / モノクローナル抗体治療 / 心臓移植 / 抗体治療
Research Abstract

The key problem encountered following organ transplantation is the allogeneic immune response, which ultimately leads to graft rejection. T cells are thought to be the main effector cells which mediate graft rejection. The activation of T cells is thought to require at least two distinct signals, antigen specific signal delivered via the TCR, as well as a co-stimulatory signal which enables the cell to proceed to IL-2 producion and proliferation. In the absence of the co-stimulatory signal, the T cell makes only a partial response and enters unresponsive state. In the present study, we investigated whether the treatment with antibodies to LFA-1 and ICAM-1 could prevent pulmonary allograft rejection in rats. In BN to LEW combination, pulmonary allograft was rejected within 7 days. In the immunohistochemical study, LFA-1-positive lymphocytes increased in the course of rejection. Two color flow cytometry analysis revealed that the intensity of LFA-1 and ICAM-1 molecules on the infiltrating T cells in the allograft increased. In the cardiac allograft, treatment with antibodies to LFA-1 and ICAM-1 could not prevent graft rejection completely. However graft survival of rats with mAbs was longer than that of rats without treatment. We are now investigating the ettects of mAbs in pulmonary transplantation.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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