Cell surface expression of MHC class I antigen is suppressed in indoleamine 2,3-dioxygenase genetically modified keratinocytes: implications in allogeneic skin substitute engraftment

Abstract

Indoleamine 2,3-dioxygenase (IDO) has been indicated to prevent the fetus from maternal T-cell rejection. A longer survival of IDO genetically modified islets transplanted into NOD mouse kidney capsules has also been demonstrated. As IDO mediated mechanism of graft protection has not been elucidated, in our study we hypothesize that the expression of IDO may prevent immune rejection by suppressing the major histocompatibility complex (MHC) class I antigen. To test this hypothesis, an IDO adenoviral vector was constructed and the effect of IDO on MHC class I expression was evaluated on recombinant adenoviral transfected keratinocytes. Following a successful construction of IDO expressing adenoviral vector, the catabolic activity of IDO enzyme was evaluated by measuring the levels of its product, kynurenine in keratinocyte conditioned medium. The results indicated a higher level of kynurenine in IDO expressing cells relative to those of control cells. The results of MHC class I experiments revealed a significant downregulation of cell membrane associated MHC class I antigen in IDO genetically modified keratinocytes relative to that of either nontransfected or empty vector transfected cells. Further experiments demonstrated that an addition of tryptophan or IDO inhibitor markedly restored the expression of MHC class I on IDO transfected keratinocytes. The findings of this study suggest that downregulation of MHC class I expression by IDO might be one of the mechanisms through which IDO mediates local immunosuppression.