Abstract
Natural killer T (NKT) cells are unique unconventional T cells that are reactive to lipid antigens presented on the non-polymorphic major histocompatibility class (MHC) I-like molecule CD1d. They have characteristics of both innate and adaptive immune cells, and have potent immunoregulatory roles in tumor immunity, autoimmunity, and infectious diseases. Based on their T cell receptor (TCR) expression, NKT cells are divided into two subsets, type I NKT cells with an invariant TCRα-chain (Vα24 in humans, Vα14 in mice) and type II NKT cells with diverse TCRs. While type I NKT cells are well-studied, knowledge about type II NKT cells is still limited, and it is to date only possible to identify subsets of this population. However, recent advances have shown that both type I and type II NKT cells play important roles in many inflammatory situations, and can sometimes regulate the functions of each other. Type II NKT cells can be both protective and pathogenic. Here, we review current knowledge on type II NKT cells and their functions in different disease settings and how these cells can influence immunological outcomes.
Highlights
Conventional major histocompatibility class (MHC)-restricted T cells have been the main attraction for immunologists, unconventional T cells are continuously gaining increased attention
Recent publications have further established that type II Natural killer T (NKT) cells are activated and potentially involved in several human diseases, while their targeting in mouse disease models have provided promising results
Type II NKT cells are activated by a range of lipid antigens, and different type II NKT T cell receptor (TCR) recognize the same lipids, the TCR repertoire is oligoclonal in nature
Summary
Conventional MHC-restricted T cells have been the main attraction for immunologists, unconventional T cells are continuously gaining increased attention Despite of their low frequencies compared to conventional T cells, the subsets of unconventional T cells play an important role in various autoimmune diseases, cancers and infections, and are present both in human and mice. These cells include CD1d-restricted NKT cells, γδ TCR expressing T cells, and MR1-restricted mucosal associated invariant T cells [1]. We discuss recent progress in the study of type II NKT cells and their critical role in different disease settings
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