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  • Original Article
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Pre-Clinical Studies

Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc− mouse model

Bone Marrow Transplantation volume 47, pages 439–450 (2012)Cite this article

Abstract

The efficacy of IVIG in preventing GvHD has not been definitely demonstrated clinically. Using a xenogeneic model of GvHD in NOD/SCID/γc− (NSG) mice, we showed that weekly administration of IVIG significantly reduced the incidence and associated mortality of GvHD to a degree similar to CsA. Unlike CsA and OKT3, IVIG were not associated with inhibition of human T-cell proliferation in mice. Instead, IVIG significantly inhibited the secretion of human IL-17, IL-2, IFN-γ and IL-15 suggesting that IVIG prevented GvHD by immunomodulation. Furthermore, the pattern of modification of the human cytokine storm differed from that observed with CsA and OKT3. Finally, in a humanized mouse model of immune reconstitution, in which NSG mice were engrafted with human CD34+ stem cells, IVIG transiently inhibited B-cell reconstitution, whereas peripheral T-cell reconstitution and thymopoiesis were unaffected. Together these in vivo data raise debate related to the appropriateness of IVIG in GvHD prophylaxis. In addition, this model provides an opportunity to further elucidate the precise mechanism(s) by which IVIG inhibit GvHD.

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Acknowledgements

This research was supported by a Bayer-Talecris-Canadian Blood Services-Héma-Québec Partnership Fund to EH (‘Mechanisms of action of Intravenous Immunoglobulins (IVIG) on Graft versus Host Disease and their influence on immune reconstitution after cord blood transplantation by using a new in vivo model of humanized NOD/SCID/γc− mice’), a Fonds de Recherche en Santé du Québec where EH was co-applicant (‘Greffe de sang de cordon: exploration des déterminants moléculaires de la prise de greffe et de la reconstitution immunitaire et mise au point de nouveaux traitements des complications grâce à des modèles précliniques’) and an Investigator Initiated Trial, funded by Talecris Biotherapeutics to EH (‘Efficacy and mechanisms of action of immunoglobulins in graft versus host disease and impact on immune reconstitution following cord blood transplantation in a humanized mice model’). JGG received a scholarship from the Fondation de l’Hôpital Sainte-Justine/Fondation des Étoiles.

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  1. CHU Sainte-Justine Research Center, Center de Cancérologie Charles-Bruneau, Montréal, Québec, Canada

    J Gregoire-Gauthier, L Durrieu, A Duval, F Fontaine, M M Dieng, M Bourgey, N Patey-Mariaud de Serre, I Louis & E Haddad

  2. Department of Pathology, CHU Sainte-Justine, Québec, Canada

    N Patey-Mariaud de Serre

  3. Department of Paediatrics, Université de Montréal, Québec, Canada

    I Louis & E Haddad

  4. Department of Microbiology and Immunology, Université de Montréal, Montréal, Québec, Canada

    E Haddad

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  1. J Gregoire-Gauthier
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EH received honoraria from CSL Behring as a member of adboard committee.

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Gregoire-Gauthier, J., Durrieu, L., Duval, A. et al. Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc− mouse model. Bone Marrow Transplant 47, 439–450 (2012). https://doi.org/10.1038/bmt.2011.93

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