Plitnick Lisa M, Herzyk Danuta J
Methods Mol Biol. 2010;598:159-71. doi: 10.1007/978-1-60761-401-2_11.
Central to the evaluation of potential immunotoxicants is the concept that measurement of multiple parameters is required for the determination of toxicity toward the immune system. A carefully considered integration of endpoints involved in the immune response should be used to determine an immunotoxic effect. A functional evaluation, specifically the rodent T-cell-dependent antibody response (TDAR) model developed for regulated immunotoxicity evaluations, has been established to detect potential immunotoxicity, especially immunosuppression, caused by chemicals and novel pharmaceuticals in development. This chapter provides an overview and detailed procedures involved in the TDAR assay that measures the immune response (i.e., antibody production) to an introduced antigen (i.e., keyhole limpet hemocyanin (KLH)) in rats or mice treated with a chemical (e.g., a known immunotoxicant and/or a new drug candidate). The TDAR model of competent immune function requires the participation of multiple effector cells such as antigen presenting cells, T lymphocytes, and B lymphocytes to produce the final product, the antigen-specific antibody response. Thus, alterations in the level of antibody production to the specific antigen may reflect effects on any or all of the cell populations involved in TDAR.
评估潜在免疫毒性物质的核心概念是,确定对免疫系统的毒性需要测量多个参数。应通过仔细考虑免疫反应中涉及的终点指标来综合判断免疫毒性效应。为规范免疫毒性评估而建立的功能评估方法,特别是啮齿动物T细胞依赖性抗体反应(TDAR)模型,已用于检测化学物质和正在研发的新型药物所引起的潜在免疫毒性,尤其是免疫抑制作用。本章概述了TDAR试验的相关内容及详细步骤,该试验用于测量经化学物质(如已知免疫毒性物质和/或新药候选物)处理的大鼠或小鼠对引入抗原(即钥孔血蓝蛋白(KLH))的免疫反应(即抗体产生)。具有正常免疫功能的TDAR模型需要多种效应细胞参与,如抗原呈递细胞、T淋巴细胞和B淋巴细胞,才能产生最终产物——抗原特异性抗体反应。因此,针对特定抗原的抗体产生水平的变化可能反映对参与TDAR的任何或所有细胞群体的影响。