Spontaneous development of pancreatitis in the MRL/Mp strain of mice in autoimmune mechanism

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Abstract
MRL/Mp mice are known to have autoimmune disease‐prone genetic background, which contributes to the development of a lethal autoimmune disease at an early age in association with the lymphoproliferative gene, Ipr. In this study, we found that MRL/Mp mice, not bearing Ipr (MRL/Mp‐+/+), spontaneously developed pancreatitis at a late stage of life, which was histopathologically characterized by destruction of pancreatic acinar cells with mononuclear cell infiltration. In female 34–38‐weeks‐old mice the incidence of pancreatitis reached 74%, whereas the male mice developed the disease with a reduced incidence, at a later stage of life and with a reduced severity. Cell infiltrates in the affected lesions were composed predominantly of CD4+ cells and to lesser extent Mac‐2+ macrophages. Adoptive transfer of the spleen cells obtained from pancreatitis‐bearing female mice generated pancreatitis in female normal mice, but not in the male mice. Transfer of the serum of pancreatitis‐bearing mice failed to induce any pancreatic lesions. These findings indicate that pancreatitis in MRL/Mp‐+/+ mice may be mediated by cellular autoimmune mechanism. This may present a useful concept for analysis of the developmental mechanisms of human chronic pancreatitis in an aspect of autoimmunity.