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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4285-4292. Prepublished online as a Blood First Edition Paper on August 27, 2007; DOI 10.1182/blood-2007-05-088286. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-05-088286v1 110/13/4285    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mateo, V. Articles by Rieux-Laucat, F. Search for Related Content PubMed PubMed Citation Articles by Mateo, V. Articles by Rieux-Laucat, F. Related Collections Immunobiology Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Perforin-dependent apoptosis functionally compensates Fas deficiency in activation-induced cell death of human T lymphocytes Véronique Mateo1,3, Michael Ménager1,3, Geneviève de Saint-Basile1,4, Marie-Claude Stolzenberg1,3, Bertrand Roquelaure5, Nicolas André5, Benoit Florkin6, Françoise le Deist4,7, Capucine Picard4, Alain Fischer1,3,8, and Frédéric Rieux-Laucat1,3 1 INSERM, U768, Paris, France; 2 Université René Descartes-Paris 5, Paris, France; 3 Hôpital Necker-Enfants Malades, Paris, France; 4 Centre d'Étude des Déficites Immunitaires, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France; 5 Multidisciplinary Department of Pediatrics, Children Hospital of La Timone, Marseille, France; 6 Département de Pédiatrie, Centre Hospitalier Universitaire de Liège, Domaine Universitaire du Sart Tilman, Liège, Belgium; 7 Département de Microbiologie et d'Immunologie, Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC; and 8 Unité d'Immunologie et Hématologie Pédiatrique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France Activation-induced cell death (AICD) is involved in peripheral tolerance by controlling the expansion of repeatedly stimulated T cells via an apoptotic Fas (CD95; APO-1)–dependent pathway. The TNFRSF-6 gene encoding Fas is mutated in children suffering from autoimmune lymphoproliferative syndrome (ALPS), which is characterized by lymphoproliferation and autoimmunity. We examined AICD in Fas-deficient T cells from ALPS patients. We showed that primary activated Fas-deficient T cells die by apoptosis after repeated T cell antigen receptor (TCR) stimulation despite resistance to Fas-mediated cell death. This Fas-independent AICD was found to be mediated through a cytotoxic granules-dependent pathway. Cytotoxic granules-mediated AICD was also detected in normal T lymphocytes though to a lesser extent. As expected, the cytotoxic granules-dependent AICD was abolished in T cells from Rab27a- or perforin-deficient patients who exhibited defective granules-dependent cytotoxicity. Supporting an in vivo relevance of the cytotoxic granules-dependent AICD in ALPS patients, we detected an increased number of circulating T lymphocytes expressing granzymes A and B. Altogether, these data indicated that the cytotoxic granules-dependent cell death in ALPS may compensate for Fas deficiency in T lymphocytes. Furthermore, they identified a novel AICD pathway as a unique alternative to Fas apoptosis in human peripheral T lymphocytes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Bristeau-Leprince, V. Mateo, A. Lim, A. Magerus-Chatinet, E. Solary, A. Fischer, F. Rieux-Laucat, and M.-L. Gougeon Human TCR {alpha}/{beta}+ CD4-CD8- Double-Negative T Cells in Patients with Autoimmune Lymphoproliferative Syndrome Express Restricted V{beta} TCR Diversity and Are Clonally Related to CD8+ T Cells J. Immunol., July 1, 2008; 181(1): 440 - 448. [Abstract] [Full Text] [PDF]

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