Endoleamine 2,3-dioxygenase expression in transplanted NOD islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes

Angela M. Alexander, Megan Crawford, Suzanne Bertera, William A. Rudert, Osamu Takikawa, Paul D. Robbins, Massimo Trucco

Research output: Contribution to journalArticlepeer-review

181 Scopus citations

Abstract

Indoleamine 2,3-dioxygenase (IDO) catalyzes the breakdown of the amino acid tryptophan into kyneurenine. It has been shown that IDO production by placental trophoblasts prevents the attack of maternal T-cells activated in response to the paternal HLA alleles expressed by the tissues of the fetus. In this article, we show that adenoviral gene transfer of IDO to pancreatic islets can sufficiently deplete culture media of tryptophan and consequently inhibit the proliferation of T-cells in vitro. Experiments in vivo have also demonstrated that transplantation of IDO-expressing islets from prediabetic NOD mouse donors into NOD-scid recipient mice is associated with a prolongation in islet graft survival after adoptive transfer of NOD diabetogenic T-cells. This protection is attributed to the depletion of tryptophan at the transplantation site beneath the kidney capsule. These results suggest that local modulation of tryptophan catabolism may be a means of facilitating islet transplantation as a therapy for type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)356-365
Number of pages10
JournalDiabetes
Volume51
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

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