The presence of CD8+ invariant NKT cells in mice

Hyunji Lee,Yoon-Kyung Park,Seokmann Hong,Junghoon Shin,Sundo Jung,Changwan Hong,Se-Ho Park,Soohwan Oh,Gap Ryol Lee

doi:10.3858/emm.2009.41.12.092

Hyunji Lee, Yoon-Kyung Park + Show 7 more

Open Access

https://doi.org/10.3858/emm.2009.41.12.092

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Abstract

Invariant natural killer T (iNKT) cells develop in the thymus upon recognition of CD1d expressed on developing thymocytes. Although CD4 and CD8 coreceptors are not directly involved in the interaction between CD1d and the T cell receptors (TCRs) of iNKT cells, a conspicuous lack of CD8(+) iNKT cells in mice raised the question of whether CD8(+) iNKT cells are excluded due to negative selection during their thymic development, or if there is no lineage commitment for the development of murine CD8(+) iNKT cells. To address this question, we analyzed iNKT cell-specific TCR V alpha 14(+) transgenic mice, where the V alpha 14 transgene forces the generation of iNKT cells. This allows detailed study of the iNKT cell repertoire. We were able to identify CD8(+) iNKT cells which respond to the NKT cell-specific glycolipid ligand alpha-galactosylceramide. Unlike conventional iNKT cells, CD8(+) iNKT cells produce predominantly IFN-gamma but not IL-4 upon antigen stimulation. We also confirmed the presence of CD8(+) iNKT cells in wild type mice. Our results suggest that CD8(+) NKT cells do exist in mice, although their population size is quite small. Their Th1-skewed phenotype might explain why the population size of this subtype needs to be controlled tightly.

Highlights

Natural killer T (NKT) cells are distinguished from conventional T lymphocytes by their function and T cell receptor (TCR) usage (Bendelac et al, 1997)
The existence of CD8+ invariant NKT (iNKT) cells in Vα14+ mice To determine the presence of CD8+ iNKT cells, we first stained splenocytes and thymocytes in CD1d-/, wild type (WT) and Vα14+ mice with α-GalCer-loaded CD1d dimer and mAbs against TCRβ, CD4 and CD8α
Because invariant TCRs of NKT cells recognize glycolipid antigens presented on CD1d, a MHC I-like molecule, coreceptor CD4 on the iNKT cells does not have any specific function for CD1d/antigen recognition, CD4 and double negative (DN) NKT cells can be functionally and developmentally distinctive (Gumperz et al, 2002; Benlagha et al, 2005)

Summary

Introduction

Natural killer T (NKT) cells are distinguished from conventional T lymphocytes by their function and T cell receptor (TCR) usage (Bendelac et al, 1997). They are divided by their TCR repertoires into 2 groups, Type I and Type II NKT cells. Type I NKT (iNKT) cells rapidly produce large amounts of cytokines such as IFN-γ, IL-4 and IL-10 upon interaction with α-GalCer-loaded CD1d (Kronenberg and Gapin, 2002; Godfrey et al, 2004) Due to their ability to produce both Th1 and Th2-type cytokines, NKT cells are believed to play roles in tumor rejection and defense against infectious agents and in the regulation of autoimmunity (Kronenberg and Gapin, 2002)

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