Nelson P A, Akselband Y, Dearborn S M, Al-Sabbagh A, Tian Z J, Gonnella P A, Zamvil S S, Chen Y, Weiner H L
AutoImmune Inc., Lexington, Massachusetts 02173, USA.
Ann N Y Acad Sci. 1996 Feb 13;778:145-55. doi: 10.1111/j.1749-6632.1996.tb21123.x.
Oral administration of myelin antigens reduces the incidence and severity of EAE in rat and mouse models and decreases the frequency of MBP-reactive cells and the frequency of attacks in some patients with multiple sclerosis. Low-dose oral tolerance has been shown to be mediated by Th2-type regulatory cells that secrete TGFbeta and IL-4/IL-10. Adjuvants and cytokines may modulate oral tolerance. The addition of betaIFN to the experimental therapy regimen, either orally or by intraperitoneal injection, has been shown to enhance the suppressive effects of oral myelin antigens when either are fed the suboptimal dosing regimen to suppress EAE. The current studies were conducted to elucidate the mechanism of the observed in vivo synergy of betaIFN and antigen feeding. Analysis of the in vitro proliferative response and cytokine production by lymphocytes from fed animals in response to specific antigen in culture shows that the synergistic effect may be related to both independent suppression of the immune response by oral betaIFN and enhanced production of TGFbeta and IL-4/IL-10. There was an unexpected increase in the production of gammaIFN by lymphocytes in vitro after three doses of oral betaIFN in vivo. These observations have important implications for the use of cytokines to modulate oral tolerance.
在大鼠和小鼠模型中，口服髓磷脂抗原可降低实验性自身免疫性脑脊髓炎（EAE）的发病率和严重程度，并减少多发性硬化症部分患者中髓鞘碱性蛋白（MBP）反应性细胞的频率以及发作频率。低剂量口服耐受已被证明由分泌转化生长因子β（TGFβ）和白细胞介素4/白细胞介素10（IL-4/IL-10）的Th2型调节细胞介导。佐剂和细胞因子可能调节口服耐受。在实验治疗方案中添加β干扰素（βIFN），无论是口服还是腹腔注射，当给予次优剂量方案以抑制EAE时，已证明可增强口服髓磷脂抗原的抑制作用。进行当前研究以阐明观察到的βIFN与抗原喂养在体内协同作用的机制。对喂食动物的淋巴细胞在体外培养中对特异性抗原的增殖反应和细胞因子产生的分析表明，协同效应可能与口服βIFN对免疫反应的独立抑制以及TGFβ和IL-4/IL-10的产生增加有关。在体内给予三剂口服βIFN后，体外淋巴细胞产生γ干扰素（γIFN）出现意外增加。这些观察结果对使用细胞因子调节口服耐受具有重要意义。
