Baker P J, Taylor C E, Stashak P W, Fauntleroy M B, Hasløv K, Qureshi N, Takayama K
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852.
Infect Immun. 1990 Sep;58(9):2862-8. doi: 10.1128/iai.58.9.2862-2868.1990.
Antibody responses of mice immunized with type III pneumococcal polysaccharide were examined with and without treatment with nontoxic lipopolysaccharide from Rhodopseudomonas sphaeroides (Rs-LPS). The results obtained were similar to those described previously for mice treated with monophosphoryl lipid A (MPL) except that lower amounts of Rs-LPS were needed. Both were without effect when given at the time of immunization with type III pneumococcal polysaccharide but elicited significant enhancement when given 2 to 3 days later. Such enhancement was T cell dependent and not due to polyclonal activation of immunoglobulin M synthesis by B cells. Treatment with either Rs-LPS or MPL abolished the expression but not induction of low-dose paralysis, a form of immunological unresponsiveness known to be mediated by suppressor T cells (Ts). The in vitro treatment of cell suspensions containing Ts with extremely small amounts of Rs-LPS or MPI completely eliminated the capacity of such cells to transfer suppression to other mice. These findings indicate that the immunomodulatory effects of both MPL and Rs-LPS are mainly the result of eliminating the inhibitors effects of Ts; this permits the positive effects of amplifier T cells to be more fully expressed, thereby resulting in an increased antibody response. The significance of these and other findings to the use of Rs-LPS as a pharmacotherapeutic agent for gram-negative bacterial sepsis is discussed.
对用III型肺炎球菌多糖免疫的小鼠,在使用和不使用球形红假单胞菌无毒脂多糖(Rs-LPS)处理的情况下检测其抗体反应。得到的结果与先前描述的用单磷酰脂质A(MPL)处理的小鼠的结果相似,只是所需的Rs-LPS量较少。在用III型肺炎球菌多糖免疫时给予这两种物质均无效果,但在2至3天后给予则会引起显著增强。这种增强是T细胞依赖性的,并非由于B细胞对免疫球蛋白M合成的多克隆激活。用Rs-LPS或MPL处理可消除低剂量麻痹的表达,但不会消除其诱导,低剂量麻痹是一种已知由抑制性T细胞(Ts)介导的免疫无反应形式。用极少量的Rs-LPS或MPL对含有Ts的细胞悬液进行体外处理,可完全消除此类细胞向其他小鼠传递抑制作用的能力。这些发现表明,MPL和Rs-LPS的免疫调节作用主要是消除Ts抑制作用的结果;这使得放大T细胞的积极作用能够更充分地表达,从而导致抗体反应增强。讨论了这些及其他发现对于将Rs-LPS用作革兰氏阴性菌败血症药物治疗剂的意义。