Velez C N, Tonkonogy S L, Lichtman S N, Cho M J
Division of Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill 27599, USA.
J Drug Target. 1997;5(1):15-24. doi: 10.3109/10611869708995854.
This study was designed to exploit the ability of Peyer's patch M cells to recognize antigen-antibody complexes in the targeted delivery of a model antigen for the induction of mucosal immunity. Sensitized liposomes consisted of an entrapped model antigen, ovalbumin (OVA), and coated with unrelated antigen-antibody complexes. Sensitized liposomes were administered intrajejunally to mice either with or without monophosphoryl lipid A (MLA). Humoral immune responses were monitored in saliva, feces, serum, and bile. Mice which received sensitized liposomes showed up to 4-fold amounts of specific IgA in saliva, feces, and bile compared to controls. Transient increases in anti-OVA IgA and IgG were observed in serum. Formulations including MLA generated positive anti-OVA IgG responses in both serum and bile. In separate experiments, cell proliferation studies were performed with Peyer's patch lymphocytes harvested from mice immunized with OVA in either standard or sensitized liposomes. Lymphocytes from test mice receiving only sensitized liposomes proliferated in the presence of OVA, but not an unrelated antigen. Taken together, these results support the potential application of antigen-antibody complexes in the stimulation of mucosal immune responses and that MLA may play an important role in overcoming OVA tolerogenicity.
本研究旨在利用派尔集合淋巴结M细胞识别抗原-抗体复合物的能力，以靶向递送模型抗原来诱导黏膜免疫。致敏脂质体由包裹的模型抗原卵清蛋白（OVA）组成，并包被有不相关的抗原-抗体复合物。将致敏脂质体经空肠内给予小鼠，同时或不给予单磷酰脂质A（MLA）。监测唾液、粪便、血清和胆汁中的体液免疫反应。与对照组相比，接受致敏脂质体的小鼠在唾液、粪便和胆汁中显示出高达4倍量的特异性IgA。血清中观察到抗OVA IgA和IgG的短暂增加。包括MLA的制剂在血清和胆汁中均产生了阳性抗OVA IgG反应。在单独的实验中，对从用标准或致敏脂质体中的OVA免疫的小鼠收获的派尔集合淋巴结淋巴细胞进行细胞增殖研究。仅接受致敏脂质体的试验小鼠的淋巴细胞在OVA存在下增殖，但在不相关抗原存在下不增殖。综上所述，这些结果支持抗原-抗体复合物在刺激黏膜免疫反应中的潜在应用，并且MLA可能在克服OVA耐受性方面发挥重要作用。
