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Suppression of islet allogeneic immune response by indoleamine 2,3 dioxygenase‐expressing fibroblasts
Author(s) -
Jalili Reza B.,
Rayat Gina R.,
Rajotte Ray V.,
Ghahary Aziz
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21100
Subject(s) - indoleamine 2,3 dioxygenase , islet , pancreatic islets , immune system , in vitro , transplantation , immune tolerance , stimulation , mixed lymphocyte reaction , cancer research , immunology , bystander effect , biology , medicine , insulin , endocrinology , t cell , tryptophan , biochemistry , amino acid
Success of transplantation of pancreatic islets which is a promising way for restoring efficient insulin regulation in type 1 diabetes depends on lifelong use of immunosuppressive drugs. To eliminate the use of systemic immunosuppressive drugs for islet transplantation, we examined the potential use of a local immunosuppressive factor, indoleamine 2,3‐dioxygenase (IDO). Thus, the aim of this study was to determine whether local expression of IDO in bystander syngeneic fibroblasts could prevent islet allogeneic immune response in vitro. C57BL/6 (B6) mouse fibroblasts were induced to express IDO by either IFN‐γ treatment or transduction with an adenoviral vector and were co‐cultured with B6 mouse lymphocytes and BALB/c mouse pancreatic islets in the presence or absence of an IDO inhibitor. Proliferation of lymphocytes were then assessed using [ 3 H]‐thymidine incorporation assay. IDO‐expression by co‐cultured syngeneic fibroblasts resulted in a five‐fold decrease in lymphocyte proliferation rate upon stimulation of lymphocytes by allogeneic mouse pancreatic islets (21.9% ± 5.3 and 22.1% ± 4.9 in the preparations with IFN‐γ treated and genetically modified IDO‐expressing fibroblasts, respectively vs. 100% in control groups, P < 0.01). Allogeneic response was restored when IDO inhibitor was added to the culture indicating that suppression was due to IDO. In conclusion, this study shows that local expression of IDO by syngeneic bystander fibroblasts can suppress in vitro proliferation of lymphocytes in response to stimulation with allogeneic pancreatic islets. This local immunosuppressive function of IDO may be employed for development of a novel alternative strategy for preventing allogeneic islet graft rejection. J. Cell. Physiol. 213: 137–143, 2007. © 2007 Wiley‐Liss, Inc.