ACCELERATED ONSET OF AGE-RELATED AUTOIMMUNE LESIONS IN MRL + MICE BY OVARIECTOMY/

MRL/Mp +/+ (MRL/+) mice, not bearing the lpr gene, are known to have a ge-related autoimmune lesions in several organs such as pancreas, sali vary and lacrimal glands at 30-weeks-old or more. In this study, MRL/ mice were ovariectomized at 4-weeks-old, and their natural histories were analysed. Ovariectomy (Ovx) of MRL/+ mice led to marked accelerat ion of organ-specific autoimmune lesions exclusively in the salivary a nd lacrimal glands at 8-weeks-old or more, whereas no significant infl ammatory change was observed in the pancreas. In the vast majority of inflammatory infiltrates, CD3(+)CD4(+) T cells were predominant in bot h the salivary and lacrimal glands of Ovx-MRL/+ mice. Up-regulated exp ression of cytokine genes including IL-1 beta, TNF-alpha, IL-2, interf eron (IFN)-gamma, and IL-6 was detected in the salivary gland of Ovx-M RL/+ mice by reverse transcriptase (RT)-PCR analysis. FACS analysis of spleen cells of Ovx-mice revealed increase in I-A(k) expression on B2 20(+) cells, and autoantibody production against the salivary gland-sp ecific antigen in sera from Ovx-MRL/+ mice, but not in control mice. T hese results suggest that age-related autoimmunity in the salivary and lacrimal glands were accelerated in Ovx-MRL/+ mice, and that autoreac tive Th1 cells were activated associated with organ-specific autoantib ody production. (C) 1997 Elsevier Science Ireland Ltd.