CCR7 defines a precursor for murine iNKT cells in thymus and periphery.

Haiguang Wang,Kristin A Hogquist

doi:10.7554/elife.34793

Abstract

The precise steps of iNKT subset differentiation in the thymus and periphery have been controversial. We demonstrate here that the small proportion of thymic iNKT and mucosal associated invariant T cells that express CCR7 represent a multi-potent progenitor pool that gives rise to effector subsets within the thymus. Using intra-thymic labeling, we also showed that CCR7+ iNKT cells emigrate from the thymus in a Klf2 dependent manner, and undergo further maturation after reaching the periphery. Ccr7 deficiency impaired differentiation of iNKT effector subsets and localization to the medulla. Parabiosis and intra-thymic transfer showed that thymic NKT1 and NKT17 were resident-they were not derived from and did not contribute to the peripheral pool. Finally, each thymic iNKT effector subset produces distinct factors that influence T cell development. Our findings demonstrate how the thymus is both a source of iNKT progenitors and a unique site of tissue dependent effector cell differentiation.

Highlights

Invariant natural killer T cells are ab T cells expressing semi-invariant T cell receptors (TCR) that respond to self-lipids or foreign-lipids presented by the MHC-I like antigen-presenting molecule CD1d (Bendelac et al, 2007)
PLZFhi Invariant natural killer T (iNKT) cells have been defined as NKT2 cells, our data strongly suggested that CCR7+ PLZFhi iNKT cells had multi-lineage potential in both the thymus and periphery
PLZFhi iNKT cells comprise a mixture of progenitors and mature IL-4 producing NKT2 effector cells

Summary

Introduction

Invariant natural killer T (iNKT) cells are ab T cells expressing semi-invariant T cell receptors (TCR) that respond to self-lipids or foreign-lipids presented by the MHC-I like antigen-presenting molecule CD1d (Bendelac et al, 2007). INKT cells are positively selected in the thymus, in response to agonist interactions with self-lipid/ CD1d expressing double positive thymocytes (DP) in the thymic cortex (Egawa et al, 2005; Gapin et al, 2001; Moran et al, 2011). At this point the cells express a high level of CD24, and are considered the most immature, or ‘stage 0’. In addition to marking the precursor pool, CCR7 directs iNKT progenitor cells to localize to the thymic medulla and is required for differentiation of iNKT effector subsets. We further establish that thymic iNKT cells influence T cell development and thymic tissue homeostasis

Results

Discussion

Materials and methods

Funding Funder