Mosmann T R, Li L, Hengartner H, Kagi D, Fu W, Sad S
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
Ciba Found Symp. 1997;204:148-54; discussion 154-8. doi: 10.1002/9780470515280.ch10.
The Tc1 and Tc2 subsets of CD8+ T effector cells secrete different patterns of cytokines, but have similar functions, including perforin- and Fas-dependent cytotoxicity, and induction of delayed type hypersensitivity (DTH) reactions involving oedema and granulocytic infiltration. The characteristic cytokines of Tc1 (gamma-interferon) and Tc2 (interleukins 4 and 5) are expressed in vivo during the DTH reaction. Tc1 cells that are deficient in cytokine synthesis also induce similar levels of DTH, supporting the lack of correlation between CD8+ T cell cytokine patterns and DTH. CD8+ T cells often produce lower cytokine levels than CD4 cells because the CD8 cells kill their antigen-presenting cells before full stimulation can occur. This effect can be counteracted by increasing the frequency of stimulation, or using perforin-deficient T cells. A multiparameter analysis of cytokine effects on CD8+ T cell differentiation has been initiated, on the basis of the principle that normal immune responses involve complex cytokine mixtures. All combinations of seven cytokines were tested. In some combinations, the combined effect could not have been predicted from individual cytokine functions. Conditions were identified in which each of interleukins 4, 10 and 12 could have opposite effects on CD8+ T cell differentiation.
CD8+效应T细胞的Tc1和Tc2亚群分泌不同模式的细胞因子，但具有相似的功能，包括穿孔素和Fas依赖性细胞毒性，以及诱导涉及水肿和粒细胞浸润的迟发型超敏反应（DTH）。在DTH反应期间，Tc1（γ干扰素）和Tc2（白细胞介素4和5）的特征性细胞因子在体内表达。细胞因子合成缺陷的Tc1细胞也能诱导相似水平的DTH，这支持了CD8+T细胞细胞因子模式与DTH之间缺乏相关性。CD8+T细胞通常比CD4细胞产生更低水平的细胞因子，因为CD8细胞在完全刺激发生之前就杀死了它们的抗原呈递细胞。这种效应可以通过增加刺激频率或使用穿孔素缺陷的T细胞来抵消。基于正常免疫反应涉及复杂细胞因子混合物的原理，已经开始对细胞因子对CD8+T细胞分化的影响进行多参数分析。测试了七种细胞因子的所有组合。在某些组合中，无法从单个细胞因子的功能预测联合效应。已经确定了白细胞介素4、10和12中的每一种对CD8+T细胞分化可能产生相反作用的条件。
