Yoshida T, Hachimura S, Kaminogawa S
Department of Applied Biological Chemistry, University of Tokyo, Japan.
Clin Immunol Immunopathol. 1997 Mar;82(3):207-15. doi: 10.1006/clin.1996.4319.
The systemic immune response and tolerance induced by oral administration of various doses of bovine alpha s1-casein were examined, focusing on cytokine responses in this study. Spleen cells from mice fed low doses of antigen secreted interferon-gamma and interleukin-2 in response to in vitro antigen stimulation, indicating that a Th1-type response was induced. In these mice, the Th1 responses after subsequent immunization and boosting with the antigen were diminished. In the case of mice fed high doses of the antigen, secretion of Th1 cytokines was minimal, but systemic responses after subsequent immunization and boosting with the antigen were strongly inhibited. Active suppression was not observed at any dose. The results indicate that, in this system, low-dose feeding induced activation of Th1 cells followed by tolerization, while high-dose feeding induced profound tolerance without prior activation. Our results have implications for clinical application of oral tolerance to allergy and autoimmune disease.
本研究聚焦于细胞因子反应，检测了口服不同剂量牛αs1-酪蛋白诱导的全身免疫反应和耐受性。喂食低剂量抗原的小鼠脾脏细胞在体外抗原刺激下分泌γ干扰素和白细胞介素-2，表明诱导了Th1型反应。在这些小鼠中，后续用抗原免疫和加强免疫后的Th1反应减弱。对于喂食高剂量抗原的小鼠，Th1细胞因子的分泌极少，但后续用抗原免疫和加强免疫后的全身反应受到强烈抑制。在任何剂量下均未观察到主动抑制。结果表明，在该系统中，低剂量喂食诱导Th1细胞活化继而产生耐受，而高剂量喂食诱导深度耐受且无先前的活化。我们的结果对口服耐受在过敏和自身免疫性疾病临床应用中的意义。
