OX40 ligand regulates splenic CD8鈭?/sup> dendritic cell-induced Th2 responses in vivo
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- 作者：Fumitaka Kamachi ; Norihiro Harada ; Yoshihiko Usui ; Tamami Sakanishi ; Naoto Ishii ; Ko Okumura ; Sachiko Miyake ; Hisaya Akiba
- 关键词：OX40 ligand ; Costimulation ; Th2 response ; Dendritic cell
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：7 February, 2014
- 年：2014
- 卷：444
- 期：2
- 页码：235-240
- 全文大小：602 K
文摘
In mice, splenic conventional dendritic cells (cDCs) can be separated, based on their expression of CD8伪 into CD8鈭?/sup> and CD8+ cDCs. Although previous experiments demonstrated that injection of antigen (Ag)-pulsed CD8鈭?/sup> 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鈭?/sup> cDCs contributes to the induction of Th2 responses by Ag-pulsed CD8鈭?/sup> 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鈭?/sup> and CD8+ cDCs. OX40L expression was not observed on freshly isolated CD8鈭?/sup> 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鈭?/sup> cDC injection. Moreover, administration of anti-OX40L mAb with Ag-pulsed CD8鈭?/sup> cDCs during a secondary response also significantly inhibited Th2 cytokine production. Thus, OX40L on CD8鈭?/sup> cDCs physiologically contributes to the development of Th2 cells and secondary Th2 responses induced by Ag-pulsed CD8鈭?/sup> cDCs in vivo.