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Suppression of cytotoxic and proliferative xenogeneic T‐cell responses by transgenic expression of indoleamine 2,3‐dioxygenase
Author(s) -
Wee Janet LyeKeng,
Christiansen Dale,
Li YuQin,
Boyle William,
Sandrin Mauro S
Publication year - 2008
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2008.8
Subject(s) - indoleamine 2,3 dioxygenase , cytotoxic t cell , splenocyte , biology , immunology , immune system , t cell , cd8 , cancer research , microbiology and biotechnology , in vitro , tryptophan , biochemistry , amino acid
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‐γ 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.