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Updated: Apr 21, 2026

An Optimized Method for Isolating and Expanding Invariant Natural Killer T Cells from Mouse Spleen
Published on: October 29, 2015
The thymic microenvironment differentially regulates development and trafficking of invariant NKT cell sublineages
Michael B Drennan1, Srinath Govindarajan2, Katelijne De Wilde2
1Department of Rheumatology, Laboratory for Molecular Immunology and Inflammation, Ghent University Hospital, Ghent B-9000, Belgium; Michael.Drennan@ugent.be Dirk.Elewaut@ugent.be.
Abstract:
The regulatory role of the thymic microenvironment during trafficking and differentiation of the invariant NKT (iNKT) cell lineage remains poorly understood. In this study, we show that fractalkine receptor expression marks emigrating subpopulations of the NKT1, NKT2, and NKT17 sublineages in the thymus and peripheral organs of naive mice. Moreover, NKT1 sublineage cells can be subdivided into two subsets, namely NKT1(a) and NKT1(b), which exhibit distinct developmental and tissue-specific distribution profiles. More specifically, development and trafficking of the NKT1(a) subset are selectively dependent upon lymphotoxin (LT)α1β2-LTβ receptor-dependent differentiation of thymic stroma, whereas the NKT1(b), NKT2, and NKT17 sublineages are not. Furthermore, we identify a potential cellular source for LTα1β2 during thymic organogenesis, marked by expression of IL-7Rα, which promotes differentiation of the NKT1(a) subset in a noncell-autonomous manner. Collectively, we propose a mechanism by which thymic differentiation and retention of the NKT1 sublineage are developmentally coupled to LTα1β2-LTβ receptor-dependent thymic organogenesis.
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