Suppression of cytotoxic and proliferative xenogeneic T-cell responses by transgenic expression of indoleamine 2,3-dioxygenase.
Tryptophan catabolism initiated by the enzyme indoleamine 2,3-dioxygenase (IDO) has been postulated to be a natural regulatory mechanism for T cells. In this study, we generated a pig endothelial cell line expressing full-length human IDO (P-HuIDO) to serve as a simple model of a cellular xenogeneic graft. Splenocytes from mice primed to P-HuIDO cells were found to be as responsive to secondary stimulation as splenocytes from mice primed to parental cells. However, in T-cell proliferation assays using P-HuIDO cells as stimulators, a significant inhibition of both naive and memory xenogeneic proliferative responses was noted. Furthermore, the production of interferon-gamma and cytotoxic T lymphocyte function were also affected. When severe combined immunodeficiency mice were grafted with P-HuIDO cells, then challenged with primed splenocytes from BALB/c mice, cellular infiltration to the graft was delayed. Our findings suggest that transgenic expression of IDO in xenografts contributes to prolonged graft survival.
Wee
Janet Lye-Keng
JL
Faculty of Veterinary Science, Veterinary Preclinical Centre, The University of Melbourne, Parkville, Australia.
Christiansen
Dale
D
Li
Yu-Qin
YQ
Boyle
William
W
Sandrin
Mauro S
MS
D000220:Adaptation, Biological / Q000276:immunology; D000818:Animals; D049109:Cell Proliferation; D017690:Cell Transplantation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011995:Recombination, Genetic / Q000235:genetics*; D013154:Spleen / Q000201:enzymology / Q000276:immunology; D013552:Swine; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase