Gene therapy efficacy of CTLA4Ig on experimental autoimmune thyroiditis / 中国综合临床

ABSTRACT

Objective To investigate the therapeutic effect of CTLA4Ig gene on experimental autoimmune thyroiditis (EAT) by the use of portable synthetic costimulatory molecules of cytotoxic T lymphocyte antigen 4 (CTLA-4) antagonist (CTLA4Ig) eukaryotic expression vector.Methods Thirty C57BL/6J female mice were divided into three groups,named EAT model group (EAT,n =10),CTLA4Ig-treatment group (CTLA4Ig-EAT,n =10) and control group(n =10).At 28 day after first immunization,plasmids mixture with pCI or pCI/CTLA4Ig were injected into thyroid tissues of EAT and CTLA4Ig-EAT by surgery,respectively.Serum,thyroid tissues and spleens were collected as samples.Thyroid autoantibody and expression of interleukin (Th)1,Th2 related cytokinesby were measured by real-time quantitative PCR and ELISA.Results Compared with EAT group,the expression of CTLA-4 in thyroid of CTLA4Ig-EAT group was elevated double folds (P =0.038),and the expression of Th1 cytokine interferon γ and intercellular adhesion molecule-1 decreased significantly (P =0.016,0.042).Meanwhile,Th2 cytokine IL-4 was increased after CTLA4Ig treatment (P =0.044).The same changes were seen in spleen tissues and serum.There was no significant difference in terms of TPOAb between EAT and treated group.Conclusion Local thyroid injection of CTLA4Ig gene shows the therapeutic effect to same degree on EAT through adjusting the underlying Th1/Th2 imbalance.