Laboratory of Cellular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Nat Immunol. 2011 Jul 31;12(9):908-13. doi: 10.1038/ni.2079.
Two competing theories have been put forward to explain the role of CD4(+) T cells in priming CD8(+) memory T cells: one proposes paracrine secretion of interleukin 2 (IL-2); the other proposes the activation of antigen-presenting cells (APCs) via the costimulatory molecule CD40 and its ligand CD40L. We investigated the requirement for IL-2 by the relevant three cell types in vivo and found that CD8(+) T cells, rather than CD4(+) T cells or dendritic cells (DCs), produced the IL-2 necessary for CD8(+) T cell memory. Il2(-/-) CD4(+) T cells were able to provide help only if their ability to transmit signals via CD40L was intact. Our findings reconcile contradictory elements implicit in each model noted above by showing that CD4(+) T cells activate APCs through a CD40L-dependent mechanism to enable autocrine production of IL-2 in CD8(+) memory T cells.
两种相互竞争的理论被提出来解释 CD4(+) T 细胞在启动 CD8(+)记忆 T 细胞中的作用：一种理论提出细胞因子白细胞介素 2（IL-2）的旁分泌；另一种理论提出通过共刺激分子 CD40 及其配体 CD40L 激活抗原呈递细胞（APC）。我们研究了体内相关三种细胞类型对 IL-2 的需求，发现 CD8(+) T 细胞而不是 CD4(+) T 细胞或树突状细胞（DC）产生了启动 CD8(+) T 细胞记忆所需的 IL-2。只有当 Il2(-/-) CD4(+) T 细胞通过 CD40L 传递信号的能力完好无损时，它们才能提供帮助。我们的发现通过表明 CD4(+) T 细胞通过 CD40L 依赖性机制激活 APC，从而使 CD8(+)记忆 T 细胞能够自体产生 IL-2，调和了上述每个模型中隐含的矛盾因素。
