Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
J Leukoc Biol. 2012 Oct;92(4):883-93. doi: 10.1189/jlb.0412177. Epub 2012 Jul 13.
Alum-based adjuvants facilitate vaccine-driven humoral immunity, but their mechanism of action remains poorly understood. Herein, we report that lack of type II NKT cells is associated with intact, mature B cells but dampened humoral immunity following immunization with Alum-adsorbed T-dependent antigen. Type II NKT cells facilitated production of IL-4, IL-5, IL-10, IL-13, and antibody by LN and splenocyte cultures following Alum/antigen administration in vivo and antigen restimulation in vitro. Addition of IL-4 and IL-5 to type II NKT-deficient cultures restored in vitro antibody production. Intracellular staining revealed that Alum-primed type II NKT cells coordinated IL-4 secretion by T cells. Alum did not significantly affect CD1d expression in vivo, but addition of CD1d-blocking mAb diminished cytokine production and in vitro antibody production. Type II NKT cells therefore function as part of the Alum-sensing apparatus and in a CD1d-dependent manner, facilitate T(H)2-driven humoral immunity. This may have important consequences for understanding the mechanism of action of Alum-containing vaccines.
铝佐剂促进疫苗驱动的体液免疫，但它们的作用机制仍不清楚。本文报道称，缺乏 II 型 NKT 细胞与完整、成熟的 B 细胞有关，但在用吸附在铝佐剂上的 T 依赖性抗原免疫后，体液免疫受到抑制。在体内给予铝/抗原和体外抗原再刺激后，II 型 NKT 细胞促进 LN 和脾细胞培养物中产生 IL-4、IL-5、IL-10、IL-13 和抗体。向 II 型 NKT 缺陷型培养物中添加 IL-4 和 IL-5 可恢复体外抗体产生。细胞内染色显示，铝佐剂激活的 II 型 NKT 细胞协调 T 细胞分泌 IL-4。铝佐剂在体内对 CD1d 的表达没有显著影响，但添加 CD1d 阻断 mAb 可减少细胞因子产生和体外抗体产生。因此，II 型 NKT 细胞作为铝佐剂感应装置的一部分，并以 CD1d 依赖性方式促进 T(H)2 驱动的体液免疫。这对于理解含铝疫苗的作用机制可能具有重要意义。
