Tamoxifen alleviates disease severity and decreases double negative T cells in autoimmune MRL-lpr/lpr mice

Previous study suggested that MRL-lpr/lpr mice treated with tamoxifen (TAM) had less severe proteinuria, reduced serum titre of anti-dsDNA autoantibod ies and an increased survival rate. To investigate further the regulatory m echanisms of TAM on MRL-lpr/lpr female mice, a total dose of 200 mu g per m ice (5.5 mg/kg) was given every 2 weeks subcutaneously, while the control m ice were injected with oil only. After being treated with TAM four times, t he mice were killed and cellular functions were evaluated. The TAM-treated groups had smaller sized spleen and lymph nodes. Flow cytometric analysis o f splenocytes had a significantly lower percentage of cell number of T cell s and double negative T cells (CD4(-) CD8(-) T cells). There was no differe nce in cytokine production (interleukin (IL)-2, IL-4, IL-5, IL-10 and inter feron-gamma (IFN-gamma)) from splenocytes stimulated with concanavalin A (C on A) or cytokines (IL-6) secreted by peritoneal exudate cells when stimula ted with lipopolysaccharide (LPS). However, IL-2 from lymph node cells was significantly higher on TAM-treated mice. Finally, splenocytes or purified T cells stimulated with anti-CD3 antibody plus cross-linking immunoglobulin G (IgG) of the TAM-treated group had higher H-3-incorporation of prolifera tion assay compared with that of control groups. In vitro study further dem onstrated that IL-2-activated proliferation of lymph node double negative ( DN) T cells can be inhibited by TAM treatment in a dose-dependent manner. O ur finding demonstrated that TAM may potentially influence T cells and modu late the immune function, which offers a novel approach to explore the Feas ibility of hormone therapy for autoimmune diseases.