title: Role of IFN-gamma in induction of Foxp3 and conversion of CD4+ CD25- T cells to CD4+ Tregs.
abstract: IFN-gamma is an important Th1 proinflammatory cytokine and has a paradoxical effect on EAE in which disease susceptibility is unexpectedly heightened in IFN-gamma-deficient mice. In this study, we provide what we believe is new evidence indicating that IFN-gamma is critically required for the conversion of CD4+ CD25- T cells to CD4+ Tregs during EAE. In our study, the added severity of EAE in IFN-gamma knockout mice was directly associated with altered encephalitogenic T cell responses, which correlated with reduced frequency and function of CD4+ CD25+ Foxp3+ Tregs when compared with those of WT mice. It was demonstrated in both human and mouse systems that in vitro IFN-gamma treatment of CD4+ CD25- T cells led to conversion of CD4+ Tregs as characterized by increased expression of Foxp3 and enhanced regulatory function. Mouse CD4+ CD25- T cells, when treated in vitro with IFN-gamma, acquired marked regulatory properties as evidenced by suppression of EAE by adoptive transfer. These findings have important implications for the understanding of the complex role of IFN-gamma in both induction and self regulation of inflammatory processes.
authors.affiliation: Joint Immunology Laboratory of Institute of Health Sciences, Shanghai JiaoTong University School of Medicine, and Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Hong
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Guangwu
authors.initials: G
authors.lastname: Xu
authors.forename: Ningli
authors.initials: N
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Ailian
authors.initials: A
authors.lastname: Liu
authors.forename: Lingyun
authors.initials: L
authors.lastname: Xu
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.forename: Jingwu Z
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000235:genetics*; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000737:chemistry; D016133:Polymerase Chain Reaction; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma