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Blood, 1 August 2008, Vol. 112, No. 3, pp. 661-671. Prepublished online as a Blood First Edition Paper on May 27, 2008; DOI 10.1182/blood-2007-10-120089. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2007-10-120089v1 112/3/661    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Laffont, S. Articles by Guéry, J.-C. PubMed PubMed Citation Articles by Laffont, S. Articles by Guéry, J.-C. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Natural killer cells recruited into lymph nodes inhibit alloreactive T-cell activation through perforin-mediated killing of donor allogeneic dendritic cells Sophie Laffont1,2, Cyril Seillet1,2, John Ortaldo3, Jérôme D. Coudert1,2, and Jean-Charles Guéry1,2 1 INSERM U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; 2 Université Paul-Sabatier, Toulouse, France; and 3 Laboratory of Experimental Immunology, National Cancer Institute-Frederick, Center for Cancer Research, Frederick, MD 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-2b) recipients injected with allogeneic BALB/c (H-2d) DCs, we demonstrated that NK cells expressing the H-2Dd-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-2d 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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