| First Author | Hongo D | Year | 2017 |
| Journal | Blood | Volume | 129 |
| Issue | 12 | Pages | 1718-1728 |
| PubMed ID | 28096089 | Mgi Jnum | J:240963 |
| Mgi Id | MGI:5896882 | Doi | 10.1182/blood-2016-07-723015 |
| Citation | Hongo D, et al. (2017) Tolerogenic interactions between CD8+ dendritic cells and NKT cells prevent rejection of bone marrow and organ grafts. Blood 129(12):1718-1728 |
| abstractText | The combination of total lymphoid irradiation and anti-T-cell antibodies safely induces immune tolerance to combined hematopoietic cell and organ allografts in humans. Our mouse model required host natural killer T (NKT) cells to induce tolerance. Because NKT cells normally depend on signals from CD8+ dendritic cells (DCs) for their activation, we used the mouse model to test the hypothesis that, after lymphoid irradiation, host CD8+ DCs play a requisite role in tolerance induction through interactions with NKT cells. Selective deficiency of either CD8+ DCs or NKT cells abrogated chimerism and organ graft acceptance. After radiation, the CD8+ DCs increased expression of surface molecules required for NKT and apoptotic cell interactions and developed suppressive immune functions, including production of indoleamine 2,3-deoxygenase. Injection of naive mice with apoptotic spleen cells generated by irradiation led to DC changes similar to those induced by lymphoid radiation, suggesting that apoptotic body ingestion by CD8+ DCs initiates tolerance induction. Tolerogenic CD8+ DCs induced the development of tolerogenic NKT cells with a marked T helper 2 cell bias that, in turn, regulated the differentiation of the DCs and suppressed rejection of the transplants. Thus, reciprocal interactions between CD8+ DCs and invariant NKT cells are required for tolerance induction in this system that was translated into a successful clinical protocol. |
