Gett Amanda V, Sallusto Federica, Lanzavecchia Antonio, Geginat Jens
Institute for Research in Biomedicine, Via Vela 6, CH-6500 Bellinzona, Switzerland.
Nat Immunol. 2003 Apr;4(4):355-60. doi: 10.1038/ni908. Epub 2003 Mar 17.
Two potential outcomes confront proliferating antigen-stimulated naive T cells: differentiation to effector and memory cells, or deletion. How stimulation affects cell fate is unclear. Autonomous CD8+ T cell differentiation has been proposed, but this does not explain the abortive proliferation of T cells induced by immature dendritic cells. Here we show that human and mouse CD4+ and CD8+ T cells receiving short or weak stimulation of the T cell receptor proliferate in response to interleukin 2 (IL-2) but are not 'fit' because they die by neglect, fail to proliferate in response to IL-7 and IL-15 and disappear in vivo. Conversely, prolonged or strong stimulation promotes 'fitness' by enhancing survival and cytokine responsiveness. Our results are consistent with the concept that signal strength drives progressive T cell differentiation and the acquisition of fitness.
增殖的抗原刺激初始T细胞面临两种潜在结果：分化为效应细胞和记忆细胞，或发生细胞凋亡。刺激如何影响细胞命运尚不清楚。有人提出了CD8+T细胞的自主分化，但这并不能解释未成熟树突状细胞诱导的T细胞增殖失败。在这里，我们表明，接受T细胞受体短时间或弱刺激的人和小鼠CD4+和CD8+T细胞会对白介素2（IL-2）作出增殖反应，但并不“健康”，因为它们会因被忽视而死亡，无法对IL-7和IL-15作出增殖反应，并在体内消失。相反，长时间或强烈的刺激通过提高存活率和细胞因子反应性来促进“健康”。我们的结果与信号强度驱动T细胞逐步分化和获得健康状态这一概念相一致。
