Suppression of cytotoxic and proliferative xenogeneic T-cell responses by transgenic expression of indoleamine 2,3-dioxygenase

Janet Wee, Dale Christiansen, Yu Quin Li, William Boyle, Mauro Sandrin

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13 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)460 - 465
Number of pages6
JournalImmunology and Cell Biology
Issue number5
Publication statusPublished - 2008
Externally publishedYes

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