Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-Cells.
J Immunol Res
; 2019: 3538963, 2019.
Article
en En
| MEDLINE
| ID: mdl-31205954
ABSTRACT
Humanized mouse models can well be modified to study specific aspects of Graft-versus-Host Disease (GvHD). This paper shows the results of both macrophage depletion and (early) B-cell depletion in a humanized mouse model using RAG2-/- γc-/- mice injected with HuPBMCs. Macrophage depletion showed a significant decrease in survival and also lead to a change in the histomorphology of the xenogeneic reaction. Higher levels of infiltrating B-cells were observed in various organs of mice depleted for macrophages. With (early) B-cell depletion using Rituximab, a clear improvement on clinical symptoms was observed, even when probably only inactivated B-cells were deleted. However, the histological examinations only showed a significant morphological effect on liver fibrosis. This may be related to a difference in the mRNA levels of TGF-ß. Also, lower mRNA levels of Tregs in some organs were observed after Rituximab treatment, which contradicts that a higher number of Tregs would always be related to less severe GvHD. Our data show that both macrophage depletion and (early) B-cell depletion in a xenogeneic mouse model can influence the clinical, histological, and cytokine production of a GvHD response.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Leucocitos Mononucleares
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Linfocitos B
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Linfocitos T Reguladores
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Trasplante de Células Madre Hematopoyéticas
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Enfermedad Injerto contra Huésped
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Cirrosis Hepática
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Macrófagos
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Immunol Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
Países Bajos