双类似物鼻黏膜耐受对预防实验性自身免疫性重症肌无力的细胞免疫调节机制

Mechanism of cellular immunity accommodation in prophylactic effects of nasal tolerance with dual analogue on experimental autoimmune myasthenia gravis in Lewis rats

目的 选择双类似物 (Lys2 6 2 Ala2 0 7)对实验性自身免疫性重症肌无力 (EAMG)模型进行鼻黏膜免疫耐受 ,探讨其对预防EAMG的细胞免疫调节机制。方法 EAMG模型在致敏前 10d(A组 )及致敏当日 (B组 )鼻腔给药 ,观察预防给药后各组间病情及细胞免疫指标的变化。结果 (1)急性期和慢性期预防耐受A、B组鼠病情明显轻于相应的对照组 ,慢性期A组明显轻于B组 ;(2 )慢性期第5 0天时CD4 + CD2 5 + T细胞含量 (单位 :cpm× 10 3 )A组 (11 34± 1 6 2 )、B组 (8 6 8± 1 83)均明显高于相应对照组 (C组 :6 78± 1 6 3,D组 :6 4 3± 1 6 9) ,且A组高于B组 ;(3)预防耐受A、B组γ 干扰素 (IFN γ)、白细胞介素 (IL) 4、IL 10阳性细胞含量均明显低于对照组 ;(4)A、B组对乙酰胆碱受体 (AchR)、Lys2 6 2 Ala2 0 7和AChR α 10 0～ 116肽段等特异性抗原的淋巴细胞的增殖反应均明显受到抑制。结论 Lys2 6 2 Ala2 0 7鼻黏膜免疫耐受抑制T细胞免疫功能 ,在防治EAMG中起重要作用。

Objective To study the mechanism of prophylactic effects of nasal tolerance with a dual analogue (Lys262-Ala207) on experimental autoimmune myasthenia gravis (EAMG). Methods Clinical and immunological changes were observed in Lewis rats administered with dual analogue Lys262-Ala207 nasally,to compare the effects between the rats with predetermined dosage of Lys262-Ala207 and control peptides at two different time points,before the day (Group A or C) or on the day (Group B or D) of immunization with acetylcholine receptor (AChR) in complete Freud′s adjuvant for 10 consecutive days. The clinical scores was evaluated for 50 days post immunization. Numbers of MNC expressing IFN-γ,IL-4 or IL-10 and CD4 + and/or CD25 + from lymph nodes were enumerated by flow cytometry. Proliferative response,expressed as stimulation index (SI),was suppressed in response to antigen-specific stimulation in the rats receiving dual analogue,as compared with the rats receiving saline buffer only. Results Group A and group B of Lewis rats developed EAMG with reduced severity,as compared to the control groups. Number of cells synthesizing IFN-γ,IL-4 or IL-10 decreased,whereas numbers of CD4 + CD25 + cells increased in group A and B than those in the control groups. Proliferative response was suppressed in response to antigen-specific stimulations in the rats receiving dual analogue Lys262-Ala207. Conclusions Nasal administ ration with a dual analogue Lys262-Ala207 at two different time points,before the day and on the day of immunization,could delay symptoms of muscular weakness in EAMG rats,which was associated with suppression of immune function in AChR antigen-specific T cells and lay a scientific foundation for treateemnt of human MG with nasal dual analogue.