Functions of CD1d-Restricted Invariant Natural Killer T Cells in Antimicrobial Immunity and Potential Applications for Infection Control.

CD1d-restricted invariant natural killer T ( i NKT) cells are innate-type lymphocytes that express a T-cell receptor (TCR) containing an invariant α chain encoded by the Vα14 gene in mice and Vα24 gene in humans. These i NKT cells recognize endogenous, microbial, and synthetic glycolipid antigens presented by the major histocompatibility complex (MHC) class I-like molecule CD1d. Upon TCR stimulation by glycolipid antigens, i NKT cells rapidly produce large amounts of cytokines, including interferon-γ (IFNγ) and interleukin-4 (IL-4). Activated i NKT cells contribute to host protection against a broad spectrum of microbial pathogens, and glycolipid-mediated stimulation of i NKT cells ameliorates many microbial infections by augmenting innate and acquired immunity. In some cases, however, antigen-activated i NKT cells exacerbate microbial infections by promoting pathogenic inflammation. Therefore, it is important to identify appropriate microbial targets for the application of i NKT cell activation as a treatment or vaccine adjuvant. Many studies have found that i NKT cell activation induces potent adjuvant activities promoting protective vaccine effects. In this review, we summarize the functions of CD1d-restricted i NKT cells in immune responses against microbial pathogens and describe the potential applications of glycolipid-mediated i NKT cell activation for preventing and controlling microbial infections.