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Indoleamine 2,3-Dioxygenase (IDO) Downregulates the Cell Surface Expression of the CD4 Molecule
Reproductive Medicine Center, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China
Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, China
Peking University Shenzhen Graduate School, Shenzhen 518000, China
Department of Gastroenterology, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, China
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 4 July 2012; in revised form: 20 August 2012 / Accepted: 21 August 2012 / Published: 30 August 2012
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.
Keywords: human IDO; CD4; T cell; immune tolerance; immune response
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Huang, G.; Zeng, Y.; Liang, P.; Zhou, C.; Zhao, S.; Huang, X.; Wu, L.; He, X. Indoleamine 2,3-Dioxygenase (IDO) Downregulates the Cell Surface Expression of the CD4 Molecule. Int. J. Mol. Sci. 2012, 13, 10863-10879.
Huang G, Zeng Y, Liang P, Zhou C, Zhao S, Huang X, Wu L, He X. Indoleamine 2,3-Dioxygenase (IDO) Downregulates the Cell Surface Expression of the CD4 Molecule. International Journal of Molecular Sciences. 2012; 13(9):10863-10879.
Huang, Guanyou; Zeng, Yaoying; Liang, Peiyan; Zhou, Congrong; Zhao, Shuyun; Huang, Xiuyan; Wu, Lingfei; He, Xianhui. 2012. "Indoleamine 2,3-Dioxygenase (IDO) Downregulates the Cell Surface Expression of the CD4 Molecule." Int. J. Mol. Sci. 13, no. 9: 10863-10879.