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

1994 Fiscal Year Final Research Report Summary

• Project/Area Number: 05670986
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Tohoku 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)
• Project Period (FY): 1993 – 1994
• Keywords: SCID mice / GVHD / CB-17 / Icr-scid Jcl / hu-PBL-SCID

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.