Anti-CD20 monoclonal antibody combined with adenovirus vector-mediated IL-10 regulates spleen CD4+/CD8+ Tcells and T-bet/GATA-3 expression in NOD mice.

Abstract

Type 1 diabetes (T1D) is an autoimmune disease characterized by a selective destruction of insulin-secreting β-cells. Both T cells and B cells serve a crucial role in pathogenesis and development of T1D. CD20 is a specific membrane antigen of B lymphocytes, while interleukin (IL)-10 is an important cytokine secreted by T helper 2 cells and has a short half-life in vivo. The combined effect of anti-CD20 and IL-10 on immune function of mice with T1D remains unknown. In the present study, 30 non-obese diabetic (NOD) mice were treated with anti-CD20 and adenoviral vector-mediated interleukin-10 (Ad-mIL-10) therapy. Alterations in CD4+, CD8+, CD4+CD25+Foxp3+ T cells, T-box expressed in T-cells (T-bet), GATA-binding protein-3 (GATA-3) interferon-γ (IFN-γ) and IL-4 were detected by flow cytometry, reverse transcription-quantitative polymerase chain reaction in NOD mice spleen tissue. The present results suggested that anti-CD20 and IL-10 treatment in NOD mice can modulate the immune functions by upregulating GATA-3 and IL-4 expression as well as downregulating T-bet and IFN-γ expression, which are involved in the pathogenesis of T1D. The current findings may provide a potential method for T1D treatment and a novel preventive therapy for T1D. Combination of anti-CD20 and Ad-mIL-10 treatment had not only immune regulatory effects but also protective effects on islet β-cells in NOD mice with T1DM at the early stages, by regulating T-bet/GATA-3 expression and Th1/Th2 cell differentiation, which has the potential for diabetes prevention and therapy.