Tanaka Yuriko, Kasai Michiyuki, Taneichi Maiko, Naito Seishiro, Kato Hiroshi, Mori Masahito, Nishida Mitsuhiro, Maekawa Naoya, Yamamura Hiroyuki, Komuro Katsutoshi, Uchida Tetsuya
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Bioconjug Chem. 2004 Jan-Feb;15(1):35-40. doi: 10.1021/bc034134o.
We previously reported that liposomes having differential lipid components displayed differential adjuvant effects when antigen was coupled with liposomes via glutaraldehyde. In the present study, antigen-liposome conjugates prepared using liposomes having differential lipid components were added to the macrophage culture, and phagocytosis and the antigen digest of liposome-coupled antigen by macrophages were then investigated. Antigen presentation by macrophages to an antigen-specific T-cell clone was further investigated using the same conjugates. Antigen-liposome conjugates which induced higher levels of antibody production in vivo were recognized more often, and the liposome-coupled antigen was digested to a greater degree by macrophages than antigen-liposome conjugates which induced lower levels of antibody production. These results correlated closely with those regarding antigen presentation by macrophages; when antigen was coupled to liposomes showing higher adjuvant effect, macrophages cocultured with antigen-liposome conjugates activated antigen-specific T-cells at a higher degree. The concentration of OVA in the macrophage culture added as antigen-liposome conjugates was approximately 32 microg/mL. However, the extent of T-cell activation was almost equal to that when 800 microg/mL of soluble OVA was added to the culture. The results of the present study demonstrated that the adjuvant activity of liposomes observed primary in vivo correlated closely with the recognition of antigen-liposome conjugates and antigen presentation of liposome-coupled antigen by macrophages, suggesting that the adjuvant effects of liposomes are exerted at the beginning of the immune response, i.e., recognition of antigen by antigen-presenting cells.
我们之前报道过，当抗原通过戊二醛与脂质体偶联时，具有不同脂质成分的脂质体表现出不同的佐剂效应。在本研究中，将使用具有不同脂质成分的脂质体制备的抗原-脂质体缀合物添加到巨噬细胞培养物中，然后研究巨噬细胞对脂质体偶联抗原的吞噬作用和抗原消化情况。使用相同的缀合物进一步研究巨噬细胞向抗原特异性T细胞克隆的抗原呈递。在体内诱导更高水平抗体产生的抗原-脂质体缀合物被识别的频率更高，并且与诱导较低水平抗体产生的抗原-脂质体缀合物相比，脂质体偶联抗原被巨噬细胞消化的程度更大。这些结果与巨噬细胞的抗原呈递结果密切相关；当抗原与显示出更高佐剂效应的脂质体偶联时，与抗原-脂质体缀合物共培养的巨噬细胞能更高程度地激活抗原特异性T细胞。作为抗原-脂质体缀合物添加到巨噬细胞培养物中的OVA浓度约为32μg/mL。然而，T细胞激活程度几乎与向培养物中添加800μg/mL可溶性OVA时相同。本研究结果表明，最初在体内观察到的脂质体佐剂活性与巨噬细胞对抗原-脂质体缀合物的识别以及脂质体偶联抗原的抗原呈递密切相关，这表明脂质体的佐剂效应在免疫反应开始时发挥作用，即抗原呈递细胞对抗原的识别。
