Myers L K, Seyer J M, Stuart J M, Kang A H
Department of Pediatrics, University of Tennessee, Memphis 38163, USA.
Immunology. 1997 Feb;90(2):161-4. doi: 10.1046/j.1365-2567.1997.00191.x.
DBA/1 mice were administered type II collagen (CII) or collagen peptides intranasally before systemic immunization to determine whether tolerance could be induced and autoimmune arthritis suppressed. Although prior experiments have demonstrated that collagen given intravenously or orally is effective, the respiratory mucosal route offers several theoretical advantages for dosing peptides, in addition to ease of use. Intact CII, CB11 and a synthetic peptide containing the immunodominant T-cell epitope recognized by H-2q mice were all effective in reducing the incidence and severity of arthritis and the immune response to CII. Since previous studies have demonstrated the importance of IgG2 antibody subclasses to the induction of collagen-induced arthritis, total immunoglobulin G (IgG), IgG1, and IgG2a and IgG2b were measured. IgG2 antibody subclasses were significantly downregulated by the treatment regimen, whereas a slight decrease in IgG1 antibodies was noted that was not significant. In an effort to determine the mechanism by which arthritis was attenuated, cervical lymph node and spleen cells from treated mice were cultured separately with CII and supernatants tested for the presence of T-cell lymphokines. The cells provided a T-helper 2 (Th2)-like response to CII, with T cells from lymph nodes secreting interleukin-4 (IL-4) and splenocytes secreting both IL-4 and IL-10, whereas a Th1-like response was detected in immunized mice not tolerized with CII. These findings indicate that the downregulation of arthritis that occurs with intranasal administration of CII is associated with Th2-type lymphokine profile and a decrease in complement-fixing antibody subclass.
在进行全身免疫之前，经鼻给DBA/1小鼠施用II型胶原蛋白（CII）或胶原蛋白肽，以确定是否可以诱导耐受性并抑制自身免疫性关节炎。尽管先前的实验已经证明静脉内或口服给予胶原蛋白是有效的，但除了使用方便之外，呼吸道粘膜途径在给药肽方面还具有几个理论优势。完整的CII、CB11以及含有H-2q小鼠识别的免疫显性T细胞表位的合成肽，在降低关节炎的发病率和严重程度以及对CII的免疫反应方面均有效。由于先前的研究已经证明IgG2抗体亚类对胶原蛋白诱导的关节炎的诱导作用很重要，因此对总免疫球蛋白G（IgG）、IgG1、IgG2a和IgG2b进行了测量。治疗方案可使IgG2抗体亚类显著下调，而IgG1抗体略有下降，但不显著。为了确定关节炎减轻的机制，将经处理小鼠的颈淋巴结和脾细胞分别与CII一起培养，并检测上清液中是否存在T细胞淋巴因子。这些细胞对CII产生了类似辅助性T细胞2（Th2）的反应，淋巴结中的T细胞分泌白细胞介素-4（IL-4），脾细胞分泌IL-4和IL-10，而在未用CII耐受的免疫小鼠中检测到类似Th1的反应。这些发现表明，经鼻施用CII后发生的关节炎下调与Th2型淋巴因子谱和补体固定抗体亚类的减少有关。
