Abstract
Recent studies suggest that murine invariant natural killer T (iNKT) cell development culminates in three terminally differentiated iNKT cell subsets denoted as NKT1, 2, and 17 cells. Although these studies corroborate the significance of the subset division model, less is known about the factors driving subset commitment in iNKT cell progenitors. In this review, we discuss the latest findings in iNKT cell development, focusing in particular on how T-cell receptor signal strength steers iNKT cell progenitors toward specific subsets and how early progenitor cells can be identified. In addition, we will discuss the essential factors for their sustenance and functionality. A picture is emerging wherein the majority of thymic iNKT cells are mature effector cells retained in the organ rather than developing precursors.
Highlights
First published: 20 Feb 2020, 9(F1000 Faculty Rev):[127]. Identified by their T-cell receptor (TCR) specificity for lipids, invariant natural killer T cells are innate-like αβ T cells capable of releasing cytokines almost instantly upon stimulation without the need for prior activation[1,2]
At the double-positive (DP) stage, their developmental programs bifurcate: While conventional αβ T cells get positively and negatively selected by thymic epithelial cells presenting peptide antigens by classical class I and II major histocompatibility complex (MHC) molecules[3,4], invariant natural killer T (iNKT) cell progenitors are selected by other DP thymocytes presenting lipid antigens by CD1d, a non-classical MHC-like molecule[5,6,7,8]
Since it is known that iNKT cell selection happens in the cortex[61], it seems likely that the interaction of stage 0 iNKT cells with CD1d/lipid-presenting DP thymocytes is the stage at which signal strength is critical (Figure 2)
Summary
F1000 Faculty Reviews are written by members of the prestigious F1000 Faculty. They are commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. Any comments on the article can be found at the end of the article
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