OX40 ligand regulates splenic CD8⁻ dendritic cell-induced Th2 responses in vivo.
In mice, splenic conventional dendritic cells (cDCs) can be separated, based on their expression of CD8α into CD8(-) and CD8(+) cDCs. Although previous experiments demonstrated that injection of antigen (Ag)-pulsed CD8(-) cDCs into mice induced CD4 T cell differentiation toward Th2 cells, the mechanism involved is unclear. In the current study, we investigated whether OX40 ligand (OX40L) on CD8(-) cDCs contributes to the induction of Th2 responses by Ag-pulsed CD8(-) cDCs in vivo, because OX40-OX40L interactions may play a preferential role in Th2 cell development. When unseparated Ag-pulsed OX40L-deficient cDCs were injected into syngeneic BALB/c mice, Th2 cytokine (IL-4, IL-5, and IL-10) production in lymph node cells was significantly reduced. Splenic cDCs were separated to CD8(-) and CD8(+) cDCs. OX40L expression was not observed on freshly isolated CD8(-) cDCs, but was induced by anti-CD40 mAb stimulation for 24 h. Administration of neutralizing anti-OX40L mAb significantly inhibited IL-4, IL-5, and IL-10 production induced by Ag-pulsed CD8(-) cDC injection. Moreover, administration of anti-OX40L mAb with Ag-pulsed CD8(-) cDCs during a secondary response also significantly inhibited Th2 cytokine production. Thus, OX40L on CD8(-) cDCs physiologically contributes to the development of Th2 cells and secondary Th2 responses induced by Ag-pulsed CD8(-) cDCs in vivo.
Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Fumitaka
F
Kamachi
Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Department of Respiratory Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Norihiro
N
Harada
Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku-ku, Tokyo 160-0023, Japan.
Yoshihiko
Y
Usui
Division of Cell Biology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Tamami
T
Sakanishi
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Naoto
N
Ishii
Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Ko
K
Okumura
Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Sachiko
S
Miyake
Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: hisaya@juntendo.ac.jp.
Hisaya
H
Akiba
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D019013:CD40 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D005260:Female; D005434:Flow Cytometry; D006433:Hemocyanins / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053278:OX40 Ligand / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016827:CD8 Antigens; D015848:Interleukin-5; D053278:OX40 Ligand; D016753:Interleukin-10; D015847:Interleukin-4; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin
Costimulation; Dendritic cell; OX40 ligand; Th2 response