Endogenous expression of B7-H4 improves long-term murine islet allograft survival

Xiaojie Wang, Jianqiang Hao, Daniel L. Metzger, Alice Mui, I. Fang Lee, Noushin Akhoundsadegh, Ziliang Ao, Lieping Chen, Dawei Ou, C. Bruce Verchere, Garth L. Warnock

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Allograft rejection is one of the main obstacles for islet transplantation. B7-H4 plays a key role in maintaining T-cell homeostasis by reducing T-cell proliferation and cytokine production. In this study, we investigated whether the endogenous expression of B7-H4 in β cells from B7-H4 transgenic mice enhances islet allograft survival. METHODS: B7-H4 transgenic C57BL/6 (B6) mice (RIP.B7-H4) were developed by inserting the entire B7-H4 open reading frame under the rat insulin promoter (RIP). B7-H4 protein expression was examined by flow cytometric analysis and immunohistochemical staining. Islet allograft survival was investigated in streptozotocin-induced diabetic recipient BALB/c (H-2d) mice transplanted with 400 islets from RIP.B7-H4 (H-2b) mice under the kidney capsule. The recipient control group received islets from wild-type B6 donors. RESULTS: B7-H4 protein was significantly up-regulated in isolated islets from RIP.B7-H4 compared with wild-type B6 mice (56%±23% vs. 3%±1.2%). B7-H4 was coexpressed with insulin, but not glucagon, suggesting that B7-H4 is expressed in a β-cell-specific manner. Recipient BALB/c mice transplanted with RIP.B7-H4 islets established euglycemia for 42.3±18.4 days (mean±SD; n=9) compared with controls at 23.1±7.8 days (mean±SD; n=12; P

Original languageEnglish (US)
Pages (from-to)94-99
Number of pages6
JournalTransplantation
Volume95
Issue number1
DOIs
StatePublished - Jan 15 2013
Externally publishedYes

Keywords

  • A-Cell functions
  • B7-H4
  • Transgenic mice

ASJC Scopus subject areas

  • Transplantation

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