Unpublished conference/Abstract (Scientific congresses and symposiums)
Rapamycin prevents experimental sclerodermatous chronic graft-versus-host disease in mice
Belle, Ludovic; Binsfeld, Marilène; DUBOIS, Sophie et al.
201238th EBMT Annual Meeting
 

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Abstract :
[en] Background: The most widely used mice model of chronic graft-versus-host disease (cGvHD) is an MHC-matched bone marrow transplantation model of sclerodermatous cGvHD. A limitation of that model is that mortality is relatively low, making difficult to study the impact of potentially therapeutic compounds. Aims: To develop a more severe model of cGVHD and to assess the impact of Rapamycin administration in that model. Results: Lethally irradiated Balb/C mice were injected with 10x106 bone marrow cells and 70x106 splenocytes from B10.D2 donor mice. Twenty-one days later, all mice developed cGvHD. For the severe model, donor B10.D2 mice were injected with 0.5x106 splenocytes from Balb/C twenty-one days before transplantation. All mice from the severe model (n=8) died a median of 32 days while 3 of 7 mice in the classical model survived beyond day 52. Mean survival was decreased in the severe model compared to the classical model (32 days versus 37 days; p=0.0185). Recipient mice in the severe group experienced higher weight loss, hair loss and skin fi brosis. Numbers of T lymphocytes (231.9 ± 151.4 versus 951 ± 532.8; p=0.0032) and CD4+ T cells (63.25 ± 41.93 versus 135.0 ± 14.39; p=0.0018) per microliter of blood at day 21 were lower in the severe group than in the classical model. Moreover, number of regulatory T cells (Tregs) was decreased in the severe model (1.250 ± 0.8864 versus 8.000 ± 6.753; p=0.0151). We then investigated whether rapamycin administration could prevent GVHD in the severe model. All (n=8) mice treated with PBS (placebo) died a median of 32 days after transplantation, while 6 of 8 mice given 1 mg/kg/day i.p. rapamycin survived beyond day 52 (p=0.0012). Number of Tregs/μl was higher at day 21 in rapamycin-treated mice than in mice given PBS (2.000±1.195 versus 1.250±0.8864; p=0.0796). Moreover, number of naïve CD4+T (10.00±4.192 versus 30.25±5.185; p= 0.0089) and effector memory T cells (EMT) (30.67±3.180 versus 67.33±7.881; p= 0.0125) were higher in rapamycin mice. Finally, proliferation of EMT (assessed by fl ow cytometry using Ki-67) was higher in PBS than in rapamycin mice (45.28%±4.084 versus 31.90%± 2.003; p=0.0474). Conclusion: We have developed a mice model of severe cGVHD. Interestingly, rapamycin prevented death from cGVHD in that model, perhaps through in vivo expansion of Treg.
Disciplines :
Hematology
Author, co-author :
Belle, Ludovic ;  Université de Liège - ULiège > GIGA-R : Hématologie
Binsfeld, Marilène ;  Université de Liège - ULiège > GIGA-R : Hématologie
DUBOIS, Sophie ;  Centre Hospitalier Universitaire de Liège - CHU > Thérapie cellulaire
Hannon, Muriel ;  Université de Liège - ULiège > GIGA-R : Hématologie
CAERS, Jo  ;  Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Briquet, Alexandra ;  Université de Liège - ULiège > GIGA-R : Hématologie
MENTEN, Catherine ;  Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
Beguin, Yves  ;  Université de Liège - ULiège > GIGA-R : Hématologie
Humblet-Baron, Stéphanie
Baron, Frédéric  ;  Université de Liège - ULiège > GIGA-R : Hématologie
Language :
English
Title :
Rapamycin prevents experimental sclerodermatous chronic graft-versus-host disease in mice
Publication date :
2012
Event name :
38th EBMT Annual Meeting
Event date :
April 1-4, 2012
Audience :
International
Available on ORBi :
since 13 March 2013

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