title: Indoleamine 2,3-dioxygenase (IDO) downregulates the cell surface expression of the CD4 molecule.
abstract: Indoleamine 2,3-dioxygenase (IDO) has been implicated in preventing the fetus from undergoing maternal T cell-mediated immune responses, yet the mechanism underlying these kinds of IDO-mediated immune responses has not been fully elucidated. Since the CD4 molecule plays a central role in the onset and regulation of antigen-specific immune responses, and T cell is sensitive in the absence of tryptophan, we hypothesize that IDO may reduce cell surface CD4 expression. To test this hypothesis, an adenoviral vector-based construct IDO-EGFP was generated and the effect of IDO-EGFP on CD4 expression was determined on recombinant adenoviral infected C8166 and MT-2 cells, by flow cytometry and/or Western blot analysis. The results revealed a significant downregulation of cell membrane CD4 in pAd-IDOEGFP infected cells when compared to that of mock-infected cells or infection with empty vector pAd-EGFP. Further experiments disclosed that either an addition of tryptophan or IDO inhibitor could partly restore CD4 expression in pAd-IDOEGFP infected C8166 cells. Our findings suggest that downregulation of CD4 by IDO might be one of the mechanisms through which IDO regulates T cell-mediated immune responses.
authors.affiliation: Reproductive Medicine Center, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China.|Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, China.
authors.forename: Guanyou
authors.initials: G
authors.lastname: Huang
authors.affiliation: Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, China.
authors.forename: Yaoying
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Peking University Shenzhen Graduate School, Shenzhen 518000, China.
authors.forename: Peiyan
authors.initials: P
authors.lastname: Liang
authors.affiliation: Reproductive Medicine Center, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China.
authors.forename: Congrong
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Reproductive Medicine Center, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, China.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, China.
authors.forename: Xianhui
authors.initials: X
authors.lastname: He
mesh_terms: D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014364:Tryptophan / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D014364:Tryptophan
keywords: CD4; T cell; human IDO; immune response; immune tolerance