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Natural killer cells recruited into lymph nodes inhibit alloreactive T-cell activation through perforin-mediated killing of donor allogeneic dendritic cells.: NK-mediated allogeneic DC killing in lymph nodes

Abstract : 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.
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https://www.hal.inserm.fr/inserm-00306011
Contributor : Jean-Charles Guéry <>
Submitted on : Friday, July 25, 2008 - 10:53:43 AM
Last modification on : Wednesday, November 18, 2020 - 5:38:03 PM
Long-term archiving on: : Tuesday, June 28, 2011 - 11:02:51 AM

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Sophie Laffont, Cyril Seillet, John Ortaldo, Jérôme Coudert, Jean-Charles Guéry. Natural killer cells recruited into lymph nodes inhibit alloreactive T-cell activation through perforin-mediated killing of donor allogeneic dendritic cells.: NK-mediated allogeneic DC killing in lymph nodes. Blood, American Society of Hematology, 2008, 112 (3), pp.661-71. ⟨10.1182/blood-2007-10-120089⟩. ⟨inserm-00306011⟩

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