| First Author | Laffont S | Year | 2008 |
| Journal | Blood | Volume | 112 |
| Issue | 3 | Pages | 661-71 |
| PubMed ID | 18505782 | Mgi Jnum | J:138424 |
| Mgi Id | MGI:3805146 | Doi | 10.1182/blood-2007-10-120089 |
| Citation | Laffont S, et al. (2008) Natural killer cells recruited into lymph nodes inhibit alloreactive T-cell activation through perforin-mediated killing of donor allogeneic dendritic cells. Blood 112(3):661-71 |
| abstractText | Natural killer (NK)-cell alloreactivity is exploited in bone marrow transplantation to improve clinical outcome. Likewise, in solid organ transplantation, it has been recently shown that recipient NK cells may limit alloreactive T-cell responses through their capacity to prevent the persistence of graft-derived allogeneic dendritic cells (DCs). In a model of CD4(+) T cell-mediated allogeneic skin graft rejection, we show that the absence of host NK-cell alloreactivity was characterized by enhanced expansion of alloreactive effector T lymphocytes, including Th2 cells, and massive eosinophilic infiltrates in the rejected tissues. In CD8(+) T cell-deficient C57BL/6 (H-2(b)) recipients injected with allogeneic BALB/c (H-2(d)) DCs, we demonstrated that NK cells expressing the H-2D(d)-specific Ly49D activating receptor were implicated in the regulation of alloreactive CD4(+) T-cell responses. Moreover, we showed that Ly49D(+) CD127(-) NK cells were recruited within DC draining lymph nodes and rapidly eliminated allogeneic H-2(d) DCs through the perforin pathway. In normal mice, we further demonstrated that NK cells by quickly eliminating allogeneic DCs strongly inhibited alloreactive CD8(+) T-cell responses. Thus, NK cells act as early regulators of alloreactive T-cell priming in allotransplantation through their capacity to kill allogeneic DCs in draining lymph nodes. |
