Clinical immunology

A Griscelli syndrome type 2 murine model of hemophagocytic lymphohistiocytosis (HLH)

  1. Jana Pachlopnik Schmid1,2,3,*,
  2. Chen-Hsuan Ho1,2,
  3. Julien Diana4,
  4. Gérard Pivert5,
  5. Agnès Lehuen4,
  6. Frédéric Geissmann5,6,
  7. Alain Fischer1,2,3,
  8. Geneviève de Saint Basile1,2,3

Article first published online: 7 NOV 2008

DOI: 10.1002/eji.200838488

Issue

European Journal of Immunology

European Journal of Immunology

Volume 38, Issue 11, pages 3219–3225, November 2008

Additional Information

How to Cite

Pachlopnik Schmid, J., Ho, C.-H., Diana, J., Pivert, G., Lehuen, A., Geissmann, F., Fischer, A. and de Saint Basile, G. (2008), A Griscelli syndrome type 2 murine model of hemophagocytic lymphohistiocytosis (HLH). Eur. J. Immunol., 38: 3219–3225. doi: 10.1002/eji.200838488

Author Information

  1. 1

    Institut National de la Santé et de la Recherche Médicale U768, Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Paris, France

  2. 2

    Faculté de Médecine de l'Université René Descartes, Institut Fédératif de Recherche Necker Enfants-Malades (IFR94), Université Paris Descartes, Paris, France

  3. 3

    Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Unité d'Immunologie et Hématologie Pédiatrique, Paris, France

  4. 4

    Institut National de la Santé et de la Recherche Médicale U561, Hôpital Saint Vincent de Paul, Paris, France

  5. 5

    Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Service d'Anatomie et de Cytologie Pathologiques, Paris, France

  6. 6

    Faculté de Médecine de l'Université René Descartes, Institut National de la Santé et de la Recherche Médicale U838, Hôpital Necker-Enfants Malades, Paris, France

*INSERM U768, Hôpital Necker Enfants-Malades, 149 rue de Sèvres, 75015 Paris, France Fax: +33-1-42-73-06-40

Publication History

  1. Issue published online: 7 NOV 2008
  2. Article first published online: 7 NOV 2008
  3. Manuscript Accepted: 27 AUG 2008
  4. Manuscript Revised: 25 AUG 2008
  5. Manuscript Received: 8 MAY 2008

Funded by

  • Institut National de la Santé et de la Recherche Médicale (INSERM)
  • Agence Nationale de la Recherche. Grant Numbers: ANR-05-MIM-010, BLAN06-3_145379
  • Fondation pour la Recherche Médicale (Equipe labélisée FRM 2007)
  • Swiss Foundation for Grants in Medicine and Biology (SSMBS, Swiss National Science Foundation). Grant Number: 1211/PASMA-110658/1
  • Fondazione Ettore e Valeria Rossi

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Keywords:

  • Animal models;
  • Clinical immunology;
  • Cytotoxicity;
  • Immunodeficiencies

Abstract

Griscelli syndrome type 2 is caused by mutations in the RAB27A gene and is a rare and potentially fatal immune disorder associated with hemophagocytic lymphohistiocytosis (HLH). Animal models could provide assistance for better understanding the mechanisms and finding new treatments. Rab27a-deficient (ashen) mice do not spontaneously develop HLH. When injected with lymphocytic choriomeningitis virus (LCMV) strain WE, Rab27a-deficient C57BL/6 mice developed wasting disease, hypothermia, splenomegaly, cytopenia (anemia, neutropenia and thrombocytopenia), hypertriglyceridemia and increased levels of IFN-γ, TNF-α, GM-CSF, IL-12, CCL5 and IL-10. Activated macrophages with hemophagocytosis were found in liver sections of these mice. Compared with perforin-deficient mice, LCMV-infected Rab27a-deficient mice showed a substantially better survival rate and slightly higher viral doses were needed to trigger HLH in Rab27a-deficient mice. This study demonstrates that LCMV-infected Rab27a-deficient C57BL/6 mice develop features consistent with HLH and, therefore, represent a murine model of HLH in human Griscelli syndrome type 2.

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