Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
J Immunol. 2011 Aug 1;187(3):1091-5. doi: 10.4049/jimmunol.1100853. Epub 2011 Jun 29.
Follicular helper T (T(FH)) cells are critical for germinal center (GC) formation. The processes that drive their generation and effector potential remain unclear. In this study, we define requirements for MHC class II APCs in murine T(FH) cell formation by either transiently ablating or restricting Ag presentation to dendritic cells (DCs). We find that cognate interactions with DCs are necessary and sufficient to prime CD4(+) T cells toward a CXCR5(+)ICOS(+)Bcl6(+) T(FH) cell intermediate. However, in the absence of additional APCs, these T(FH) cells fail to produce IL-21. Furthermore, in vitro priming of naive T cells by B cells engenders optimal production of IL-21, which induces a GC B cell transcriptional profile. These results support a multistep model for effector T(FH) cell priming and GC initiation, in which DCs are necessary and sufficient to induce a T(FH) cell intermediate that requires additional interactions with distinct APCs for full effector function.
滤泡辅助 T（T（FH））细胞对于生发中心（GC）的形成至关重要。但其产生和效应功能的驱动过程仍不清楚。在这项研究中，我们通过瞬时消融或限制抗原呈递给树突状细胞（DC），来定义 MHC Ⅱ类 APC 在小鼠 T（FH）细胞形成中的要求。我们发现与 DC 的同源相互作用对于将 CD4（+）T 细胞向 CXCR5（+）ICOS（+）Bcl6（+）T（FH）细胞中间状态的诱导是必需且充分的。然而，在没有其他 APC 的情况下，这些 T（FH）细胞无法产生 IL-21。此外，B 细胞对幼稚 T 细胞的体外诱导可产生最佳的 IL-21 产量，从而诱导 GC B 细胞的转录谱。这些结果支持了效应 T（FH）细胞的诱导和 GC 起始的多步模型，其中 DC 是必需且充分的，可诱导 T（FH）细胞中间状态，该状态需要与其他 APC 的进一步相互作用才能发挥完全的效应功能。
