Immunoregulatory function of gut intraepithelial lymphocytes during tolerance induction of liver allografts

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671219
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: YOKOI Yoshihiro Hamamatsu Univ. Sch. Of Med., Dept. of Sug. II, Instructor, 医学部附属病院, 助手 (80313956)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Satoshi Hamamatsu Univ. Sch. Of Med., Dept. of Sug. II, Professor, 医学部, 教授 (00090027) ; SUZUKI Shohachi Hamamatsu Univ. Sch. Of Med., Dept. of Sug. II, Assistant Professor, 医学部附属病院, 助手 (20196827)
• Project Period (FY): 2000 – 2002
• Keywords: gut intraepithelial lymphocytes / liver allograft tolerance / interleukin-10 / transforming growth factor-β / immunoregulation

Research Abstract

Background : Although the intraepithelial lymphocytes (IELs) constitute gut associated-lymphoid tissues which represent the largest immune system in the body, their role in the induction of liver allograft tolerance remains unknown. Methods : DA rats orthotopically transplanted with Lewis liver allografts and Lewis rats grafted with DA livers were used as tolerogenic and immunogenic combinations, respectively. We serially followed the phenotypic changes of the IELs from the recipients and specifically focused on their immunological function on day 7 after the transplantation. Results : There were no differences in the changes of proportion of T and B cell repertoires (αβ-TCR, CD4, CD8, OX33, and γδ-TCR) in the IELs between tolerogenic and immunogenic recipients. However, the messenger RNA (mRNA) expression of transforming growth factor-β and interleukin-10 was markedly enhanced on the IELs in tolerogenic, but not in immunogenic recipients. Adoptive transfer of IELs from tolerogenic recipients rendered indefinite survival of heart allografts in DA recipients (n=6), whereas the same manipulation was not successful by those cells from immunogenic recipients. The IELs exerted immunosuppressive function earlier after the operation than the splenocytes, because adoptive transfer of the splenocytes was successful in only half of the heart allografts (n=3 of 6). Irradiation of liver allografts prior to implantation abrogated the presentation of unique cytokine mRNA profile and the successful adoptive transfer of the tolerogenic IELs, concomitant with deletion of chimeric cells in the intestinal epithelium. Conclusions : IELs play an immunoregulatory role in the induction of liver allografts, which might be mediated by interaction with radiosenstive passenger leukocytes migrating into the intestinal microenvironment.