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Publication : OX40 ligand regulates splenic CD8⁻ dendritic cell-induced Th2 responses in vivo.

First Author  Kamachi F Year  2014
Journal  Biochem Biophys Res Commun Volume  444
Issue  2 Pages  235-40
PubMed ID  24462862 Mgi Jnum  J:218141
Mgi Id  MGI:5616713 Doi  10.1016/j.bbrc.2014.01.060
Citation  Kamachi F, et al. (2014) OX40 ligand regulates splenic CD8(-) dendritic cell-induced Th2 responses in vivo. Biochem Biophys Res Commun 444(2):235-40
abstractText  In mice, splenic conventional dendritic cells (cDCs) can be separated, based on their expression of CD8alpha 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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