Geldhof A B, Moser M, Lespagnard L, Thielemans K, De Baetselier P
Laboratory of Cellular Immunology, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel (VUB), Brussels,
Blood. 1998 Jan 1;91(1):196-206.
Activation of natural killer (NK) cells in the presence of interleukin-12 (IL-12) augments the capacity of these effector cells to recognize B7-1- and B7-2-expressing target cells. These effector cells also efficiently lyse autologous B7-positive progenitor or organ-derived dendritic cells, suggesting a physiologic regulatory pathway between IL-12, NK cells, and B7-expressing antigen-presenting cells. Although IL-12-activated NK cells secreted higher levels of interferon-gamma, this cytokine did not play a role in synergistic effects of IL-12 and B7 on NK activation. The B7-counterreceptor was found to be selectively upregulated on IL-2/IL-12 as compared with IL-2-activated NK cells. CD28 is functionally involved in the recognition of B7 on target cells since IL-2/IL-12-activated NK cells derived from CD28 knockout mice were strongly reduced in their capacity to lyse syngeneic B7-positive tumor cells as well as antigen-presenting cells. However, recognition of B7 on allogeneic targets did not require the expression of CD28 on the IL-2/IL-12-activated NK cells. Hence, IL-12 triggers the expression of both CD28-dependent and CD28-independent mechanisms that allow NK cells to eliminate B7-positive target cells including autologous dendritic cells.
在白细胞介素-12（IL-12）存在的情况下，自然杀伤（NK）细胞的激活增强了这些效应细胞识别表达B7-1和B7-2的靶细胞的能力。这些效应细胞还能有效地裂解自体B7阳性祖细胞或器官来源的树突状细胞，提示IL-12、NK细胞和表达B7的抗原呈递细胞之间存在生理调节途径。虽然IL-12激活的NK细胞分泌更高水平的干扰素-γ，但这种细胞因子在IL-12和B7对NK激活的协同作用中不起作用。与IL-2激活的NK细胞相比，发现B7反受体在IL-2/IL-12激活的NK细胞上选择性上调。CD28在功能上参与对靶细胞上B7的识别，因为源自CD28基因敲除小鼠的IL-2/IL-12激活的NK细胞裂解同基因B7阳性肿瘤细胞以及抗原呈递细胞的能力大大降低。然而，对异基因靶细胞上B7的识别并不需要IL-2/IL-12激活的NK细胞表达CD28。因此，IL-12触发了CD28依赖性和CD28非依赖性机制的表达，使NK细胞能够消除包括自体树突状细胞在内的B7阳性靶细胞。
