1. Rapid destruction of encapsulated islet xenografts by NOD mice is CD4-dependent and facilitated by B-cells: innate immunity and autoimmunity do not play significant roles
- Author
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Weiming Yu, Bao-You Xu, Hua Yang, Rebecca Macintosh, James R. Wright, and David V. Serreze
- Subjects
CD4-Positive T-Lymphocytes ,Graft Rejection ,Male ,medicine.medical_specialty ,Time Factors ,Transplantation, Heterologous ,Islets of Langerhans Transplantation ,Mice, Nude ,Inflammation ,Autoimmunity ,Nod ,Biology ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,Islets of Langerhans ,Mice ,Mice, Inbred NOD ,Internal medicine ,medicine ,Animals ,Lymphocytes ,NOD mice ,Mice, Knockout ,Transplantation ,geography ,Mice, Inbred BALB C ,Innate immune system ,geography.geographical_feature_category ,Macrophages ,Graft Survival ,Islet ,Lymphocyte Subsets ,Microspheres ,Eosinophils ,Endocrinology ,Treatment Outcome ,Immunology ,CD4 Antigens ,Female ,medicine.symptom ,CD8 - Abstract
Background. Spontaneously diabetic NOD mice rapidly reject microencapsulated islet xenografts via an intense pericapsular inflammatory response. Methods. Tilapia (fish) islets were encapsulated in 1.5% alginate gel microspheres. Recipients in series 1 were spontaneously diabetic NOD mice and streptozotocin-diabetic nude, euthymic Balb/c, prediabetic NOD, and NOR (a recombinant congenic strain not prone to autoimmune diabetes) mice. Recipients in Series 2 were STZ-diabetic NOD, NOD-scid, NOD CD4 T-cell KO, NOD CD8 T-cell KO, and NOD B-cell KO mice. Results. In Series 1, encapsulated fish islet grafts uniformly survived long-term in nude mice but were rejected in Balb/c and, at a markedly accelerated rate, in spontaneously diabetic NOD, streptozotocin-diabetic NOD and NOR recipients. Histologically, intense inflammation (macrophages and eosinophils) surrounding the microcapsules was seen only in NOD and NOR recipients. In Series 2, encapsulated fish islets uniformly survived long-term in NOD-scid and NOD CD4 KO mice; graft survival was markedly prolonged in B-cell KO (P
- Published
- 2005