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The Journal of Immunology, 2006, 177: 934-943.
Copyright © 2006 by The American Association of Immunologists

Novel Function of IFN-{gamma}: Negative Regulation of Dendritic Cell Migration and T Cell Priming1

Xiaodong Wu2,*, Wanqiu Hou2,*, Shuhui Sun{dagger}, Enguang Bi*, Yuan Wang*, Mude Shi*, Jingwu Zang{ddagger}, Chen Dong§,|| and Bing Sun3,*,||

* Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai, China; {dagger} Fudan University School of Medicine, Shanghai, China; {ddagger} Health Science Institute, Shanghai Institute of Biological Sciences, Shanghai, China; § Department of Immunology, M. D. Anderson Cancer Center, Houston, TX 77030; Laboratory of Molecular Virology, Institute Pasteur of Shanghai, CAS, Shanghai, China; and || Immunology Division, E-Institutes of Shanghai Universities, Shanghai, China

IFN-{gamma} is considered to be a Th1 cytokine with immunomodulatory effects on a variety of immune cells. In this study, we determined whether dendritic cell (DC) function was aberrant in IFN-{gamma} knockout (GKO) mice. The results demonstrated that IFN-{gamma} deficiency did not interfere with bone marrow-derived DC development and maturation in vitro. However, functional analysis showed that bone marrow-derived DC from GKO mice had altered cytokine secretion, allostimulatory and Ag presentation capacity, chemokine receptor expression, and in vitro chemotaxis. LPS induced the recruitment of DC from different organs into the spleen; epicutaneously sensitized DC with hapten (FITC) accumulated in the draining lymph nodes and CD11c+ DC levels in the draining lymph nodes from autoantigen (interphotoreceptor retinoid-binding protein) immunized mice were enhanced in GKO mice as compared with wild-type mice. After treatment of GKO mice with i.p. IFN-{gamma} injection restored IFN-{gamma} levels in vivo, DC migration decreased in response to LPS or FITC. IFN-{gamma} altered the adaptive immune responses in vivo, since T cell priming and IL-2 production were increased in interphotoreceptor retinoid-binding protein-immunized GKO mice. Furthermore, in IFN-{gamma}-treated GKO mice, experimental autoimmune uveitis score enhancement and T cell activation were eliminated. Taken together, IFN-{gamma} appears to play a negative regulatory role on in vivo DC function, resulting in suppression of Ag-specific T cell priming.




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