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

• Published in: Immunology 2000-05, Vol.100 (1), p.110-118
• Main Authors: Wu, W.‐M., Suen, J.‐L., Lin, B.‐F., Chiang, B.‐L.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Surface - metabolism; Ascitic Fluid - immunology; Autoimmune Diseases - drug therapy; Autoimmune Diseases - immunology; Cell Culture Techniques; Cell Division - drug effects; Cell Division - immunology; Dose-Response Relationship, Immunologic; Estrogen Antagonists - therapeutic use; Female; Interleukin-2 - immunology; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - immunology; Lymph Nodes - immunology; Mice; Original; Proteinuria - drug therapy; Spleen - immunology; Survival Rate; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; tamoxifen; Tamoxifen - therapeutic use
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1046/j.1365-2567.2000.00998.x

Summary Previous study suggested that MRL‐lpr/lpr mice treated with tamoxifen (TAM) had less severe proteinuria, reduced serum titre of anti‐dsDNA autoantibodies and an increased survival rate. To investigate further the regulatory mechanisms of TAM on MRL‐lpr/lpr female mice, a total dose of 200 µg per mice (5·5 mg/kg) was given every 2 weeks subcutaneously, while the control mice were injected with oil only. After being treated with TAM four times, the mice were killed and cellular functions were evaluated. The TAM‐treated groups had smaller sized spleen and lymph nodes. Flow cytometric analysis of splenocytes had a significantly lower percentage of cell number of T cells and double negative T cells (CD4– CD8– T cells). There was no difference in cytokine production (interleukin (IL)‐2, IL‐4, IL‐5, IL‐10 and interferon‐γ (IFN‐γ)) from splenocytes stimulated with concanavalin A (Con A) or cytokines (IL‐6) secreted by peritoneal exudate cells when stimulated 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 3H‐incorporation of proliferation assay compared with that of control groups. In vitro study further demonstrated that IL‐2‐activated proliferation of lymph node double negative (DN) T cells can be inhibited by TAM treatment in a dose‐dependent manner. Our finding demonstrated that TAM may potentially influence T cells and modulate the immune function, which offers a novel approach to explore the feasibility of hormone therapy for autoimmune diseases.