Islet xenograft destruction in the hu-PBL-severe combined immunodeficient (SCID) mouse necessitates anti-CD3 preactivation of human immune cells.
Clin Exp Immunol
; 121(3): 557-65, 2000 Sep.
Article
en En
| MEDLINE
| ID: mdl-10971525
Introduction of the hu-PBL-SCID mouse model has yielded a potentially useful tool for research in transplantation. The aim of this study was to define the conditions necessary for a reconstituted human immune system to destroy in a consistent manner rat islet xenografts in the alloxan-diabetic hu-PBL-SCID mouse. We examined different time points of hu-PBL reconstitution, different transplantation sites of the islets and several hu-PBL reconstitution protocols. Major differences in graft destruction were observed between the different hu-PBL reconstitution protocols, irrespective of timing of hu-PBL reconstitution or site of transplantation. Although preactivation of hu-PBL did not improve the level of hu-PBL chimerism, histological and immunohistochemical analysis of the grafts revealed a severe human lymphocytic infiltration and beta cell destruction only in the grafts of mice receiving preactivated hu-PBL. This beta cell injury resulted in impaired glucose tolerance, with in some animals recurrence of hyperglycaemia, and decreased insulin and C-peptide levels after glucose stimulation. Therefore, we conclude that activation of hu-PBL prior to transfer is essential in achieving xenograft infiltration and destruction in hu-PBL-SCID mice. The need for immune manipulation suggests that interactions between hu-PBL and xenografts in this model may be hampered by incompatibilities in cross-species adhesion and/or activation signals.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trasplante de Islotes Pancreáticos
/
Inmunodeficiencia Combinada Grave
Tipo de estudio:
Etiology_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Clin Exp Immunol
Año:
2000
Tipo del documento:
Article
País de afiliación:
Bélgica
Pais de publicación:
Reino Unido