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In vivo study of human xenogeneic immune system by SCID mice GVHD model

Research Project

Project/Area Number 05670986
Research Category

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

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionTohoku University

Principal Investigator

FUJIMORI Keisei  Tohoku University, The Second Dept.of Surgery, Research Associate, 医学部, 助手 (50238622)

Co-Investigator(Kenkyū-buntansha) DOI Hideyuki  Tohoku University, The Second Dept.of Surgery, Research Associate, 医学部附属病院, 助手 (90188839)
SATOMI Susumu  Tohoku University, The Second Dept.of Surgery, Professor, 医学部, 教授 (00154120)
佐川 純司  東北大学, 医学部附属病院, 助手 (60250784)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsSCID mice / GVHD / CB-17 / Icr-scid Jcl / hu-PBL-SCID / 照射SCIDマウス / 細胞移入 / NK細胞 / 細胞移入実験 / 細胞浸潤 / GVH反応
Research Abstract

The use of severe combined immunodeficient (SCID) mice to examine ways to introduce a xenogeneic immune system into SCID mice by taking advantage of the immune deficiency of the mice has provided an animal graft-versus-host disease (GVHD) model to examine the in vivo fanction of transferred human peripheral blood leukocytes (PBL). Transfer of human PBL has been successful or produced acute GVHD,however, the cotroversy remains regarding the capability of human PBL to develop classical symptoms of GVHD.To obtain consistent engraftment with GVHD,SCID mice were pretreated with a combination of total body irradiation (250R) anti-lymphcyte serum (ALS) and anti-asialo GM1 (anti-mouse natural killer cell) antiserum before the intraperitoneal injection of 1 X 10 (6) human PBL.With this protocol, human CD3-positive cells was 1.66-3.36% in the peripheral blood and 2.27-3.67% in the spleen. Human tumor cell lines were implanted subcutaneously or intraperitonealy into the SCID mice to estimate the take rate. The overall take rate was 0% for SCID mice. In our experiment, CB-17/Icr-scid Jcl could not accept any human cells and lines. Mortality at 2 week was 60% (3/5) in the mice bearing human cells after the treatment of irradiation and serum compared with 100% in the control mice. Histologic examination of lymphocytes engraftment of lung liver and duodenum was indistinguishable from normal control in SCID mice. In this context, the cause of death in SCID mice was thought to be the toxic effect of pretreatment rather than GVHD.Although we could not established a GVHD model with SCID mice, we have modified the method of immunoselection of cells which allows a fast positive selection viable T,B lymphocytes.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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