Natural killer T (NKT) cells in autoimmune hepatitis

Abstract

Natural killer T (NKT) cells represent an innate-like lymphocyte population endowed with unique antigen recognition and tissue distribution features. Their abundance in the microvascular compartments of the liver allows NKT cells to immediately respond to lipid antigens and soluble factors circulating through the portal vein system by releasing tremendous amounts of different cytokines and chemokines. Subsequently, dependent on the nature of the lipid antigen encountered as well as the accessory signal(s) provided, NKT cells not only contribute to the maintenance of immune tolerance, but also direct adverse immune reactions locally and systemically. Focusing on their potent immunomodulatory features and their interactions with various innate and adaptive immune cells, the role of NKT cells in perpetuating the loss of liver-specific immune tolerance will be discussed.

Figure 1

Lipid antigens as well as accessory signals provided by different antigen-presenting cell subsets define the reactivity and mobility of NKT cells in the liver. Metabolic and microbial compounds absorbed from the intestinal tract circulate into the hepatic blood circulation through the portal vein system. Different antigen presenting cells (APCs) lining the microvascular compartments of the liver take up and process these compounds. Dependent on the type of the APC lipid antigens as well as accessory signals such as cytokines or costimulatory molecules are provided to NKT cells. NKT cells patrolling the liver sinusoids release immediately cytokines and/or chemokines upon antigen encounter and shape dependent on the nature of the antigen and accessory signals provided the subsequent immune response.