Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc- mouse model
| Autor: | Ludovic Durrieu, François Fontaine, N Patey-Mariaud de Serre, Joëlle Gregoire-Gauthier, Arnaud Duval, M Bourgey, Mame Massar Dieng, Isabelle Louis, Elie Haddad |
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| Rok vydání: | 2011 |
| Předmět: |
Cell Transplantation
T-Lymphocytes Graft vs Host Disease Immunoglobulins chemical and pharmacologic phenomena Antigens CD34 Nod Mice SCID Interferon-gamma Mice Immune system Antigen In vivo Mice Inbred NOD hemic and lymphatic diseases medicine Animals Humans Cell Proliferation Interleukin-15 Transplantation biology business.industry Interleukin-17 Hematology medicine.disease Flow Cytometry Disease Models Animal surgical procedures operative Immune System Humanized mouse Immunology biology.protein Cytokines Interleukin-2 Antibody Stem cell Cytokine storm business |
| Zdroj: | Bone marrow transplantation. 47(3) |
| ISSN: | 1476-5365 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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