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Primary hemophagocytic syndromes point to a direct link between lymphocyte cytotoxicity and homeostasis

Authors

  • Gael Ménasché,

    1. INSERM U429, Hôpital Necker Enfants-Malades, Paris, France.
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  • Jérôme Feldmann,

    1. INSERM U429, Hôpital Necker Enfants-Malades, Paris, France.
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  • Alain Fischer,

    1. INSERM U429, Hôpital Necker Enfants-Malades, Paris, France.
    2. Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France.
    3. Unité d'Immunologie et Hématologie, Hôpital Necker-Enfants Malades, Paris, France.
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  • Geneviève De Saint Basile

    Corresponding author
    1. INSERM U429, Hôpital Necker Enfants-Malades, Paris, France.
    2. Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France.
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* Geneviève de Saint Basile
Unité INSERM U 429
Hôpital Necker-Enfants Malades
149 Rue de Sèvres
75015 Paris
France
Tel.: +33 1 44 49 50 80
Fax: +33 1 42 73 06 40
E-mail: sbasile@necker.fr

Abstract

Summary:  Hemophagocytic syndrome (HS) is a severe and often fatal syndrome resulting from potent and uncontrolled activation and proliferation of T-lymphocytes, leading to excessive macrophage activation and multiple deleterious effects. The onset of HS characterizes several inherited disorders in humans. In each condition, the molecular defect impairs the granule-dependent cytotoxic activity of lymphocytes, thus highlighting the determinant role of this function in driving the immune system to a state of equilibrium following infection. It has also been shown that some of the proteins required for lytic granule secretion are required for melanocyte function, leading to associated hypopigmentation in these conditions. This review focuses on several effectors of this secretory pathway, recently identified, because their defects cause these disorders, and discusses their role and molecular interactions in granule-dependent cytotoxic activity.

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