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Veillette A.,Clinical Research Institute of Montreal | Veillette A.,University of Montreal | Veillette A.,McGill University | Perez-Quintero L.-A.,Clinical Research Institute of Montreal | And 2 more authors.
Current Opinion in Allergy and Clinical Immunology | Year: 2013

Purpose of review X-linked lymphoproliferative (XLP) syndromes and related autosomal disorders are severe primary immune deficiencies triggered by infection with Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis. Recent findings reviewed herein provided key new insights into the genetic and immunological basis of these diseases. They also improved our comprehension of the immunological mechanisms controlling EBV infection. Recent findings Mutations of an X-linked gene, SH2D1A, which encodes the signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), are responsible for most cases of XLP disorders. More recently, other genetic causes for XLP syndromes and autosomal recessive variants of this disease were elucidated. Mutations in genes such as XIAP, ITK, and CD27 were identified. The clinical manifestations and immunological defects seen in these patients were characterized. Summary The similarities and differences in immunological defects and clinical manifestations between XLP syndromes and related autosomal recessive disorders enabled important new insights into the pathogenesis of these diseases. They also helped our comprehension of the mechanisms implicated in the control of EBV infection. They suggested that CD8 T cells, natural killer (NK) cells, and NKT cells are critically involved. Copyright © Lippincott Williams & Wilkins. Source


Kurowska M.,Laboratoire du Developpement Normal et Pathologique du Systeme Immunitaire | Kurowska M.,University of Paris Descartes | Kurowska M.,IMAGINE Institute | Goudin N.,University of Paris Descartes | And 19 more authors.
Blood | Year: 2012

Cytotoxic T lymphocytes kill target cells via the polarized secretion of cytotoxic granules at the immune synapse. The lytic granules are initially recruited around the polarized microtubule-organizing center. In a dynein-dependent transport process, the granules move along micro-tubules toward the microtubule-organizing center in the minus-end direction. Here, we found that a kinesin-1-dependent process is required for terminal transport and secretion of polarized lytic granule to the immune synapse. We show that synaptotagmin-like protein 3 (Slp3) is an effector of Rab27a in cytotoxic T lymphocytes and interacts with kinesin-1 through the tetratricopeptide repeat of the kinesin-1 light chain. Inhibition of the Rab27a/Slp3/kinesin-1 transport complex impairs lytic granule secretion. Our data provide further molecular insights into the key functional and regulatory mechanisms underlying the terminal transport of cytotoxic granules and the latter's secretion at the immune synapse. © 2012 by The American Society of Hematology. Source

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