Alternative pathway for the development of Vα14+ NKT cells directly from CD4-CD8- thymocytes that bypasses the CD4+CD8+ stage

Nat Immunol. 2017 Mar;18(3):274-282. doi: 10.1038/ni.3668. Epub 2017 Jan 30.

Abstract

Although invariant Vα14+ natural killer T cells (NKT cells) are thought to be generated from CD4+CD8+ double-positive (DP) thymocytes, the developmental origin of CD4-CD8- double-negative (DN) NKT cells still remains unresolved. Here we provide definitive genetic evidence obtained, through studies of mice with DP-stage-specific ablation of expression of the gene encoding the recombinase component RAG-2 (Rag2) and by a fate-mapping approach, that supports the proposal of the existence of an alternative developmental pathway through which a fraction of DN NKT cells with strong T-helper-type-1 (TH1)-biased and cytotoxic characteristics develop from late DN-stage thymocytes, bypassing the DP stage. These findings provide new insight into understanding of the development of NKT cells and propose a role for timing of expression of the invariant T cell antigen receptor in determining the functional properties of NKT cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic / genetics
  • DNA-Binding Proteins / genetics
  • Immunity, Innate
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells / physiology*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • Th1 Cells / immunology
  • Thymocytes / physiology*

Substances

  • CD4 Antigens
  • CD8 Antigens
  • Cytokines
  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta