Saparov A, Wagner F H, Zheng R, Oliver J R, Maeda H, Hockett R D, Weaver C T
Department of Pathology, University of Alabama at Birmingham, 35294, USA.
Immunity. 1999 Sep;11(3):271-80. doi: 10.1016/s1074-7613(00)80102-8.
Single cell studies have identified intraclonal heterogeneity of cytokine production by activated T cells. To investigate implications of cytokine heterogeneity for cell fate, an interleukin (IL)-2 promoter-green fluorescent protein (GFP) reporter transgenic model was developed to track IL-2+ and IL-2- T cells during differentiation from naive precursors. Antigen-activated IL-2+ and IL-2- cells had comparable proliferative capacities in primary responses. However, T cells that expressed IL-2 in primary responses demonstrated enhanced antigenic sensitivity and increased expression of effector cytokines in secondary responses in vitro and in vivo. Thus, heterogeneity of activation during a primary response translates into heterogeneous secondary responses, in which enhanced memory/effector function is linked to cells that previously exceeded an activation threshold associated with IL-2 gene transcription.
单细胞研究已确定活化T细胞产生细胞因子存在克隆内异质性。为了研究细胞因子异质性对细胞命运的影响，构建了一种白细胞介素（IL）-2启动子-绿色荧光蛋白（GFP）报告基因转基因模型，以追踪从初始前体细胞分化过程中的IL-2+和IL-2-T细胞。抗原活化的IL-2+和IL-2-细胞在初次反应中具有相当的增殖能力。然而，在初次反应中表达IL-2的T细胞在体外和体内的二次反应中表现出增强的抗原敏感性和效应细胞因子表达增加。因此，初次反应期间激活的异质性转化为异质性的二次反应，其中增强的记忆/效应功能与先前超过与IL-2基因转录相关的激活阈值的细胞相关联。
