Cytokines and Autoimmune β Cell Destruction in NOD Mouse Fetal Pancreas Isografts in

Abstract

The role of cytokines in a model of cyclophosphamide (CP)-accelerated β cell destruction in fetal pancreas isografts transplanted into NOD mice was studied. One group of prediabetic NOD mice was injected with CP at a dose of 300 mg/kg ip and 7 days later isografts of organ cultured fetal pancreas (FP) were transplanted under the kidney capsule of these and untreated control mice. The mice were killed at several time points posttransplantation and the histological appearance of the host pancreas used to evaluate the disease progress in the grafts since previous studies had shown good corellation between isograft and native pancreas pathology. Intragraft cytokine gene expression was monitored by reverse-transcriptase polymerase chain reaction (RT-PCR) at the same time points and the expression levels between the experimental groups compared to normal kidney tissue. In comparison to isografts from non-CP injected mice, isografts from CP-treated mice showed increased expression of IFN-γ, TNF-α, TNF-β, IL-5, and eotaxin but no increase in IL-10 expression. The enhanced transcription of these cytokines correlated with massive infiltration of immune cells and ongoing β cell destruction in the host pancreas of the CP-treated recipients.

Key Words:

• cytokine and chemokine mRNA
• cyclophosphamide
• RT-PCR
• NOD mice
• fetal islets grafts
• βcell destruction