Immune Tolerance in Murine Islet Transplantation Across HY Disparity

HY 항원 불일치 췌도 이식에 의한 면역 관용의 유도

  • Choi, Seung-Eun (Department of Microbiology and Immunology, Tumor Immunity Medical Research Center, Xenotransplantation Research Institute, The Transplantation Research Institute, SNUMRC, Seoul National University College of Medicine) ;
  • Park, Chung-Gyu (Department of Microbiology and Immunology, Tumor Immunity Medical Research Center, Xenotransplantation Research Institute, The Transplantation Research Institute, SNUMRC, Seoul National University College of Medicine)
  • 최승은 (서울대학교 의과대학 미생물학교실, 종양면역의과학센터, 이종장기이식연구센터, 서울대학교의학원 장기이식연구소) ;
  • 박정규 (서울대학교 의과대학 미생물학교실. 종양면역의과학센터. 이종장기이식연구센터. 서울대학교의학원 장기이식연구소)
  • Published : 2004.03.31

Abstract

Background: Minor histocompatibility HY antigen, as a transplantation antigen, has been known to cause graft rejection in MHC (major histocompatibility complex) matched donor-recipient. The aim of our study is to investigate the role of male antigen (HY) disparity on MHC matched pancreatic islet transplantation and to examine the mechanism of the immune reaction. Methods: Pancreatic islets were isolated and purified by collagen digestion followed by Ficoll gradient. The isolated islets of male C57BL6/J were transplanted underneath the kidney capsule of syngeneic female mice rendered diabetic with streptozotocine. Blood glucose was monitored for the rejection of engrafted islets. After certain period of time, tail to flank skin transplantation was performed either on mouse transplanted with HY mismatched islets or on sham treated mouse. The rejection was monitored by scoring gross pathology of the engrafted skin. Results: HY mismatched islets survived more than 300 days in 14 out of 15 mice. The acceptance of second party graft (male B6 islets) and the rejection of third party graft (male BALB/c islets) in these mice suggested the tolerance to islets with HY disparity. B6 Skin with HY disparity was rejected on day $25{\pm}7$. However, HY mismatched skin transplanted on the mice tolerated to HY mismatched islets survived more than 240 days. Tetramer staining in these mice indicated the CTL recognizing MHC Db/Uty was not deleted or anergized. Conclusion: The islet transplantation across HY disparity induced tolerance to HY antigen in C57BL6 mouse, which in turn induced tolerance to HY mismatched skin, which otherwise would be rejected within 25 days. The MHC tetramer staining suggested the underlying mechanisms would not be clonal deletion or anergy.

Keywords

Acknowledgement

Supported by : 서울대학병원

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