Odean M J, Frane C M, Van derVieren M, Tomai M A, Johnson A G
Department of Medical Microbiology/Immunology, University of Minnesota, Duluth 55812.
Infect Immun. 1990 Feb;58(2):427-32. doi: 10.1128/iai.58.2.427-432.1990.
In a previous study the adjuvant action of a monophosphoryl lipid A, a nontoxic derivative of endotoxic lipopolysaccharide (LPS), was found to be negated by a monoclonal anti-gamma interferon (anti-IFN-gamma) antibody. The present investigation centered on three other adjuvants of diverse microbial origins, testing for their capacity to affect the release of IFN-gamma as an explanation for their antibody-enhancing action. The adjuvant action of each of the three, a wild-type LPS, synthetic poly(A)-poly(U) complexes, and a synthetic muramyl dipeptide, n-acetylmuramyl-L-alanyl-D-glutaminyl-n-butyl ester (murabutide), was transferable by adjuvant-stimulated T cells to normal spleen cells on coculture. Supernatant fluids from these T cells contained increased levels of IFN-gamma. Addition of a monoclonal anti-IFN-gamma antibody to adjuvant-stimulated spleen cell cultures reduced the adjuvant action by approximately one-half. Removal of natural killer cells from spleen cell populations prior to culture with antigen had no effect on the enhancement induced by LPS and monophosphoryl lipid A. It was concluded that the enhancement induced by the adjuvants LPS, poly(A)-poly(U), and murabutide is mediated in part by their action on T cells resulting in release of IFN-gamma suggesting activation of a common transmembrane signal.
在先前的一项研究中发现，单磷酰脂质A（一种内毒素脂多糖（LPS）的无毒衍生物）的佐剂作用被单克隆抗γ干扰素（抗IFN-γ）抗体所抵消。本研究集中于其他三种来源各异的佐剂，测试它们影响IFN-γ释放的能力，以此解释它们增强抗体的作用。这三种佐剂分别是野生型LPS、合成的聚（A）-聚（U）复合物以及合成的胞壁酰二肽N-乙酰胞壁酰-L-丙氨酰-D-谷氨酰胺-n-丁酯（murabutide），它们的佐剂作用可通过佐剂刺激的T细胞在共培养时传递给正常脾细胞。这些T细胞的上清液中IFN-γ水平升高。向佐剂刺激的脾细胞培养物中添加单克隆抗IFN-γ抗体可使佐剂作用降低约一半。在用抗原培养之前从脾细胞群体中去除自然杀伤细胞，对LPS和单磷酰脂质A诱导的增强作用没有影响。得出的结论是，佐剂LPS、聚（A）-聚（U）和murabutide诱导的增强作用部分是通过它们对T细胞的作用介导的，导致IFN-γ释放，这表明激活了一种共同的跨膜信号。
