Mechanisms of Transfer into SCID Mice Reconstituted with Tissue-infiltrating Cells from Murine Model for Sjoegren's Syndrome.

Abstract

To elucidate the mechanism during reconstitution of murine organ-specific autoimmune lesions developing in the salivary and lacrimal gland from MRL/lpr mice into severe combined immunodeficiency (SCID) mice, mice which received salivary gland inflammatory cells from MRL/lpr mice were analyzed for cytokine gene expressions and autoantibody production. Successful transfer of autoimmune lesions developed at 8 wk after the intraperitoneal injection of 1X106 cells. Flow cytometric analysis using peripheral blood mononuclear cells (PBMC) from transferred SCID mice was investigated every wk after the injection until 8 wk. Peripheral CD 4+ T cells were detected at 2 wk or more after the injection and their number gradually increased in the periphery. RT-PCR analysis on PBMC revealed that cytokine gene expressions including IL-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-6, IL-10, IL-12 (p 40) were detected at 8 wk after the injection. The number of peripheral B220+ B cells increased on PBMC during reconstitution in transferred SCID mice. Autoantibody production specific for the salivary gland was detected in sera from transferred SCID mice at 2 wk or more. These results suggest that cytokine gene stimulation and autoantibody production are involved in the development of organ-specific autoimmune lesions during reconstitution in transferred SCID mice.