HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eidenschenk, C. Articles by Casanova, J.-L. Search for Related Content PubMed PubMed Citation Articles by Eidenschenk, C. Articles by Casanova, J.-L.

Familial NK Cell Deficiency Associated with Impaired IL-2- and IL-15-Dependent Survival of Lymphocytes¹

Céline Eidenschenk^*, Emmanuelle Jouanguy^*, Alexandre Alcaïs^*, Jean-Jacques Mention, Benoit Pasquier, Ingrid M. Fleckenstein, Anne Puel^*, Laure Gineau^*, Jean-Claude Carel^¶, Eric Vivier^||, Françoise Le Deist^#,** and Jean-Laurent Casanova^2,*,#

^* Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes-Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 550, Faculté de Médecine Necker, Paris, France, European Union (EU); Interaction de l’épithélium intestinal avec le système immunitaire, INSERM Equipe Mixte 0212, Faculté de Médecine Necker, Paris, France, EU; Développement Normal et Pathologique du Système Immunitaire, INSERM Unité 429, Hôpital Necker Enfants Malades, Pavillon Kirmisson, Paris, France, EU; Institut für Klinische und Molekulare Virologie, Friedrich-Alexander, Universität Erlangen-Nürnberg, Erlangen, Germany, EU; ^¶ Département d’Endocrinologie Pédiatrique et INSERM Unité 561, Groupe Hospitalier Cochin-Saint Vincent de Paul et Faculté de Médecine Cochin, Université de Paris René Descartes, Paris, France, EU; ^|| Centre d’Immunologie de Marseille-Luminy, INSERM-Centre National de la Recherche Scientifique-Université Méditerranée, Marseille, France, EU; ^# Centre d’étude des Déficits Immunitaires, Hôpital Necker Enfants Malades, Paris, France, EU, and Unité d’Immunologie et d’Hématologie Pédiatriques, Hôpital Necker Enfants Malades, Paris, France, EU; and ^** Département de Microbiologie et d’Immunologie, Hôpital Sainte Justine 3175, Côte Sainte Catherine Montréal, Canada

We previously reported the clinical phenotype of two siblings with a novel inherited developmental and immunodeficiency syndrome consisting of severe intrauterine growth retardation and the impaired development of specific lymphoid lineages, including transient CD8 T lymphopenia and a persistent lack of blood NK cells. We describe here the elucidation of a plausible underlying pathogenic mechanism, with a cellular phenotype of impaired survival of both fresh and herpesvirus saimiri-transformed T cells, in the surviving child. Clearly, NK cells could not be studied. However, peripheral blood T lymphocytes displayed excessive apoptosis ex vivo. Moreover, the survival rates of CD4 and CD8 T cell blasts generated in vitro, and herpesvirus saimiri-transformed T cells cultured in vitro, were low, but not nil, following treatment with IL-2 and IL-15. In contrast, Fas-mediated activation-induced cell death was not enhanced, indicating a selective excess of cytokine deprivation-mediated apoptosis. In keeping with the known roles of IL-2 and IL-15 in the development of NK and CD8 T cells in the mouse model, these data suggest that an impaired, but not abolished, survival response to IL-2 and IL-15 accounts for the persistent lack of NK cells and the transient CD8 T lymphopenia documented in vivo. Impaired cytokine-mediated lymphocyte survival is likely to be the pathogenic mechanism underlying this novel form of inherited and selective NK deficiency in humans.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ C.E. was supported by La Fondation pour la Recherche Médicale, France, European Union (EU). A.A. was supported by L’Assistance-Publique-Hopitaux de Paris, France, EU. The Laboratory of Human Genetics of Infectious Diseases was supported by the Schlumberger Foundation, the Banque Nationale de Paris-Paribas Foundation, the Institut Universitaire de France, and EU Grant QLK2-CT-2002-00846. J.-L.C. is an International Scholar of the Howard Hughes Medical Institute.

² Address correspondence and reprint requests to Dr. Jean-Laurent Casanova, Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes-Institut National de la Santé et de la Recherche Médicale Unité 550, Faculté de Médecine Necker, 156 rue de Vaugirard, 75015 Paris, France, European Union. E-mail address: casanova{at}necker.fr

³ Abbreviations used in this paper: 7AAD, 7-aminoactinomycin D; GH, growth hormone; SAB, AB serum; PMN, polymorphonuclear neutrophil; mTOR, mammalian target of rapamycin.

This article has been cited by other articles:

				S.-Y. Zhang, E. Jouanguy, S. Ugolini, A. Smahi, G. Elain, P. Romero, D. Segal, V. Sancho-Shimizu, L. Lorenzo, A. Puel, et al. TLR3 Deficiency in Patients with Herpes Simplex Encephalitis Science, September 14, 2007; 317(5844): 1522 - 1527. [Abstract] [Full Text] [PDF]