Type II NKT cells facilitate Alum-sensing and humoral immunity

Abstract

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_H2‐driven humoral immunity. This may have important consequences for understanding the mechanism of action of Alum‐containing vaccines.