Novel function of IFN-gamma: negative regulation of dendritic cell migration and T cell priming.
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.
Wu
Xiaodong
X
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences (CAS), 320 Yueyang Road, Shanghai 200031, China.
Hou
Wanqiu
W
Sun
Shuhui
S
Bi
Enguang
E
Wang
Yuan
Y
Shi
Mude
M
Zang
Jingwu
J
Dong
Chen
C
Sun
Bing
B
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001327:Autoimmune Diseases / Q000517:prevention & control; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage; D006241:Haptens / Q000008:administration & dosage* / Q000276:immunology; D007371:Interferon-gamma / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019707:Receptors, Chemokine / Q000096:biosynthesis; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014606:Uveitis, Anterior / Q000276:immunology / Q000517:prevention & control
D016207:Cytokines; D006241:Haptens; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016650:Fluorescein-5-isothiocyanate