title: CD8alpha+ dendritic cells enhance the antigen-specific CD4+ T-cell response and accelerate development of collagen-induced arthritis.
abstract: To investigate the role of CD8alpha(+) DCs in the development of collagen-induced arthritis (CIA). The immunogenic properties of CD8alpha(+) and CD8alpha(-) DC subsets were investigated by mixed-lymphocyte reaction and cytokine enzyme-linked immunoassay. CII-pulsed CD8alpha(+) DCs or CD8alpha(-) DCs with CD4(+) T cells from CIA mice were adoptively transferred onto the hind footpad of DBA mice. The onset of arthritis and the arthritis index were examined for 14 weeks after adoptive transfer. Expression of MHC-II and CD80 but not CD86 and CD40 was higher in CD8alpha(+) DCs than in CD8alpha(-) DCs from the spleens of CIA mice. Culturing CD8alpha(+) DCs with CD4(+) T cells significantly increased the proliferative response of CD4(+) T cells in the presence of CII. The production of interleukin (IL)-12p70, IL-17, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha was slightly increased in CD8alpha(+) DCs than in CD8alpha(-) DCs. DBA/1 mice that were adoptively transferred with CII-pulsed CD8alpha(+) DCs and CD4(+) T cells into the footpads showed accelerated onset of CIA compared to control group. By contrast, CD8alpha(-) DCs showed a partial inhibitory effect on CIA. These findings show that CD8alpha(+) DCs accelerated the onset of CIA when aoptively transferred with CD4(+) T cells and that CD8alpha(+) DCs provoke the development of CIA probably by stimulating the immune responses of CII-reactive CD4(+) T cells and by increasing the production of inflammatory cytokines.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Kang-Nam Sacred Heart Hospital, Hallym University, Seoul, Republic of Korea.
authors.forename: Young Ok
authors.initials: YO
authors.lastname: Jung
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Min
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Ju-Youn
authors.initials: JY
authors.lastname: Jeon
authors.forename: Jae-Sun
authors.initials: JS
authors.lastname: Lee
authors.forename: Hye-Joa
authors.initials: HJ
authors.lastname: Oh
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Kang
authors.forename: Hyun-Sil
authors.initials: HS
authors.lastname: Park
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Seok Goo
authors.initials: SG
authors.lastname: Cho
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D033023:Foot Joints / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA
chemical_list: D015703:Antigens, CD; D016827:CD8 Antigens; D016207:Cytokines