Suppression of experimental autoimmune uveoretinitis by regulatory dendritic cells in mice.
OBJECTIVE
To examine the effects of bone marrow-derived regulatory dendritic cells (DCs) with potent immunoregulatory properties on the development of experimental autoimmune uveoretinitis (EAU).


METHODS
Bone marrow cells obtained from C57BL/6 mice were treated with granulocyte-macrophage colony-stimulating factor, transforming growth factor beta, and interleukin (IL) 10 and stimulated with lipopolysaccharide to produce mature and regulatory DCs. Expression of major histocompatibility complex and costimulatory molecules was analyzed by flow cytometry. Then EAU was induced by immunization with human interphotoreceptor retinoid-binding protein (hIRBP) peptide 1-20, followed by intravenous injection of hIRBP peptide-pulsed regulatory DCs. Control mice received transforming growth factor beta and IL-10 nontreated mature DC or phosphate-buffered saline. We evaluated EAU clinically and histopathologically. Immunologic responses to hIRBP peptide were assessed by delayed-type hypersensitivity and T-cell proliferation and cytokine production.


RESULTS
Regulatory DCs expressed comparable levels of major histocompatibility complex class II molecules but reduced levels of CD80, CD86, and CD40 compared with mature DCs. Delayed-type hypersensitivity to hIRBP peptide and the development of EAU were markedly suppressed in mice receiving regulatory DCs compared with control mice. Lymph node cells from regulatory DC-treated mice showed significantly reduced hIRBP-specific T-cell proliferation and interferon gamma production but increased IL-10 production.


CONCLUSIONS
Administration of regulatory DCs potentially inhibited the development of EAU.


CONCLUSIONS
Application of regulatory DCs may be a novel candidate for immunotherapy for human endogenous uveitis.
Usui
Yoshihiko
Y
Department of Ophthalmology, Tokyo Medical University, 6-7-1, Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Takeuchi
Masaru
M
Hattori
Takaaki
T
Okunuki
Yoko
Y
Nagasawa
Kazumi
K
Kezuka
Takeshi
T
Okumura
Ko
K
Yagita
Hideo
H
Akiba
Hisaya
H
Goto
Hiroshi
H
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D019013:CD40 Antigens / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005136:Eye Proteins; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D007165:Immunosuppression Therapy; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins; D018417:Th1 Cells / Q000276:immunology; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D005136:Eye Proteins; D000949:Histocompatibility Antigens Class II; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial