Pier G B, Markham R B
J Immunol. 1982 May;128(5):2121-5.
The effect of the cytotoxic drug vinblastine on the development of immunity to high m.w. polysaccharide (PS) isolated from culture supernates of Pseudomonas aeruginosa was investigated. One microgram of PS, a normally nonimmunogenic, nonprotective dose, plus 75 micrograms of vinblastine were administered to BALB/c mice, and afforded protection to live organism challenge with the homologous strain. The kinetics and serotype specificity of the immune response indicated an active immunization had occurred. Analyses of serum antibody levels of mice given the PS-drug regimen in a sensitive, radioactive antigen-binding assay (RABA) failed to show development of antibody to the immunizing PS. Immunity could be passively transferred with spleen cells but not by serum from PS-drug-immunized animals, and the effector cell was removed by antisera to the Thy-1.2 antigen. Nu/nu mice were also protected against challenge after immunization with PS and vinblastine, but this protection was observed in association with the development of serum antibody to PS in these mice, as measured in the RABA. Protective immunity could not be elicited in the BALB/c mice by PS plus cyclophosphamide. These data suggest that under certain conditions, PS antigens can elicit T cell-dependent immune phenomena, and this T cell-dependent immunity can protect mice from live organism challenge against an extracellular bacterial pathogen.
研究了细胞毒性药物长春碱对小鼠针对从铜绿假单胞菌培养上清液中分离出的高分子量多糖(PS)产生免疫反应的影响。给BALB/c小鼠注射1微克通常无免疫原性、无保护作用剂量的PS以及75微克长春碱,可使其在受到同源菌株活体攻击时得到保护。免疫反应的动力学和血清型特异性表明发生了主动免疫。在灵敏的放射性抗原结合试验(RABA)中,对接受PS-药物方案处理的小鼠血清抗体水平进行分析,未显示出针对免疫用PS产生抗体。免疫可通过脾细胞被动转移,但不能通过PS-药物免疫动物的血清被动转移,且效应细胞可被抗Thy-1.2抗原的抗血清清除。裸鼠在用PS和长春碱免疫后也能抵御攻击,但在RABA检测中,这些小鼠血清中针对PS的抗体产生时可观察到这种保护作用。PS加环磷酰胺不能在BALB/c小鼠中引发保护性免疫。这些数据表明,在某些条件下,PS抗原可引发T细胞依赖性免疫现象,且这种T细胞依赖性免疫可保护小鼠免受细胞外细菌病原体的活体攻击。