Natural killer cells recruited into lymph nodes inhibit alloreactive T-cell activation through perforin-mediated killing of donor allogeneic dendritic cells. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Blood Year : 2008

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

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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Dates and versions

inserm-00306011 , version 1 (25-07-2008)

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Sophie Laffont, Cyril Seillet, John Ortaldo, Jérôme D. 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, 2008, 112 (3), pp.661-71. ⟨10.1182/blood-2007-10-120089⟩. ⟨inserm-00306011⟩
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