Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Graduate Program in Immunology, Harvard Medical School, Boston, MA 02115, USA.
Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Cell Rep. 2020 May 26;31(8):107679. doi: 10.1016/j.celrep.2020.107679.
Generating robust CD4 T-helper cell type 1 (Th1) responses is essential for protective vaccine-induced type 1 immunity. Here, we examine whether immunization formulation associated with enhanced vaccine efficacy promotes antigen targeting and cell recruitment into lymph node (LN) niches associated with optimal type 1 responses. Immunization with antigen and Toll-like receptor agonist emulsified in oil leads to an increased differentiation of IFNγ/TNF-α polyfunctional Th1 cells compared to an identical immunization in saline. Oil immunization results in a rapid delivery and persistence of antigen in interfollicular regions (IFRs) of the LN, whereas without oil, antigen is distributed in the medullary region. Following oil immunization, CXCL10-producing inflammatory monocytes accumulate in the IFR, which mobilizes antigen-specific CD4 T cells into this niche. In this microenvironment, CD4 T cells are advantageously positioned to encounter arriving IL-12-producing inflammatory dendritic cells (DCs). These data suggest that formulations delivering antigen to the LN IFR create an inflammatory niche that can improve vaccine efficacy.
产生强大的 CD4 辅助性 T 细胞 1（Th1）反应对于保护性疫苗诱导的 1 型免疫至关重要。在这里，我们研究了与增强疫苗功效相关的免疫制剂是否促进了抗原靶向和细胞募集到与最佳 1 型反应相关的淋巴结（LN）小生境。与在盐水中进行相同的免疫接种相比，用油乳化的抗原和 Toll 样受体激动剂进行免疫接种会导致 IFNγ/TNF-α 多功能 Th1 细胞的分化增加。油免疫接种导致抗原在 LN 的滤泡间区（IFR）中快速传递和持续存在，而没有油时，抗原则分布在髓质区。在油免疫接种后，产生 CXCL10 的炎症性单核细胞在 IFR 中积聚，这将抗原特异性 CD4 T 细胞动员到这个小生境中。在这个微环境中，CD4 T 细胞处于有利位置，可以与到达的产生 IL-12 的炎症性树突状细胞（DC）相遇。这些数据表明，将抗原递送到 LN IFR 的制剂可以创建一个炎症小生境，从而提高疫苗的功效。
