Administration of donor splenocytes via the respiratory tract generates CD8α+ regulatory dendritic cells and induces hyporesponsiveness to fully allogeneic cardiac grafts
| Autor: | Masanori Niimi, Nobuo Shinohara, Daiki Iwami, Nozomu Shirasugi, Osamu Aramaki |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer Lipopolysaccharide Immunology chemical and pharmacologic phenomena 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Allograft survival Splenocyte Immunology and Allergy Medicine Transplantation business.industry In vitro body regions 030104 developmental biology medicine.anatomical_structure chemistry Under-stimulation business psychological phenomena and processes 030215 immunology Respiratory tract |
| Zdroj: | Transplant Immunology. 50:60-67 |
| ISSN: | 0966-3274 |
| DOI: | 10.1016/j.trim.2018.07.001 |
| Popis: | Background We previously showed that pretreatment with intratracheal delivery (ITD) of alloantigen induced prolonged cardiac allograft survival and generated regulatory T cells (Tregs) in mice. In this study, we examined the role of splenic dendritic cells (DCs) in the ITD model. Methods CBA mice were treated with ITD from C57BL/10 splenocytes and 7 days later received transplantation of C57BL/10 hearts. In adoptive transfer studies, splenic DCs from ITD-treated mice were transferred into naive CBA recipients that received C57BL/10 hearts immediately after the transfer. In addition, to determine the role of splenic DCs isolated from ITD-treated mice, the cells were incubated under stimulation with lipopolysaccharide (LPS). Results ITD-treated CBA recipients had markedly prolonged allograft survival (median survival time [MST], 67 days) while naive recipients rejected allografts acutely (MST, 8 days). In adoptive transfer studies, CBA recipients of the transfer of splenic DCs from ITD-treated mice had prolonged allograft survival (MST, 85 days), while CBA recipients of the transfer of splenic DCs from naive mice did not have prolonged allograft survival (MST, 8 days). In another transfer study, CBA recipients of the transfer of splenic CD8α+ DCs from ITD-treated mice had prolonged allograft survival (MST, 79 days), while those receiving splenic CD8α− DCs from ITD-treated mice did not have prolonged allograft survival (MST, 8 days). In vitro studies showed that ITD-treated splenic DCs produced more IL-10 and less IL-12 than naive splenic DCs under stimulation with LPS. Conclusions ITD pretreatment induces regulatory DCs, which produce high amounts of IL-10 resulting in the prolongation of graft survival in our model. |
| Databáze: | OpenAIRE |
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