Immune Netw.  2004 Mar;4(1):53-59. 10.4110/in.2004.4.1.53.

Immune Tolerance in Murine Islet Transplantation Across HY Disparity

• Choi SE
• Park CG

• KMID: 2054244
• DOI: http://doi.org/10.4110/in.2004.4.1.53

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 +/- 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.

Keyword

Minor histocompatibility; HY disparity; islet transplantation; skin transplantation; immune tolerance

MeSH Terms

Animals
Blood Glucose
Clonal Deletion
Collagen
Digestion
Female
Ficoll
Graft Rejection
H-Y Antigen
Histocompatibility
Humans
Immune Tolerance*
Islets of Langerhans
Islets of Langerhans Transplantation*
Kidney
Male
Mice
Pathology
Skin
Skin Transplantation
Streptozocin
Tail
Transplants
Blood Glucose
Collagen
Ficoll
H-Y Antigen
Streptozocin