Local expression of B7-H4 by recombinant adenovirus transduction in mouse islets prolongs allograft survival

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

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND.: Allogeneic pancreatic islet transplantation has the potential to cure type 1 diabetes. One of the barriers to islet transplantation is the alloreactive T-cell response between donors and recipients. Costimulatory molecules, which play a major role in the regulation of the immune response to antigens during graft rejection, may be used to inhibit allograft destruction. B7-H4 is one such member in the costimulatory family, which has established negative regulatory function of T-cell responses. METHODS.: To determine whether local expression of B7-H4 protein can protect β cells from damage in islet allotransplantation, we have constructed a recombinant adenovirus expressing a B7-H4 complementary deoxyribonucleic acid (Ad-B7-H4). To study the in vivo effects of B7-H4 expression on islet graft survival, adenovirus-transduced islets from donor Balb/c mice were transplanted into streptozotocin-diabetic C57BL/6 mice (n=12). RESULTS.: Expression of B7-H4 in islets by Ad-B7-H4 transduction at an optimized condition did not inhibit glucose-stimulated insulin secretion of the treated islets. The recipient mice transplanted with Ad-B7-H4-transduced islets established euglycemia for a longer time (mean 56.5 days), compared with control mice transplanted with Ad-LacZ-transduced islets (mean 14.5 days, [n=12, P

Original languageEnglish (US)
Pages (from-to)482-490
Number of pages9
JournalTransplantation
Volume87
Issue number4
DOIs
StatePublished - Feb 27 2009

Keywords

  • B7-H4
  • Costimulatory molecules
  • Islet allograft rejection
  • Type 1 diabetes

ASJC Scopus subject areas

  • Transplantation

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