OX40 ligand regulates splenic CD8 dendritic cell-induced Th2 responses in vivo |
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Authors: | Fumitaka Kamachi Norihiro Harada Yoshihiko Usui Tamami Sakanishi Naoto Ishii Ko Okumura Sachiko Miyake Hisaya Akiba |
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Institution: | 1. Department of Immunology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan;2. Department of Respiratory Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan;3. Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku-ku, Tokyo 160-0023, Japan;4. Division of Cell Biology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan;5. Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan |
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Abstract: | 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. |
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Keywords: | OX40 ligand Costimulation Th2 response Dendritic cell |
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