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T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse.

The ability of antigen receptors to engage self-ligands with varying affinity is crucial for lymphocyte development. To further explore this concept, we generated transgenic mice expressing GFP from the immediate early gene Nr4a1 (Nur77) locus. GFP was up-regulated in lymphocytes by antigen receptor stimulation but not by inflammatory stimuli. In T cells, GFP was induced during positive selection, required major histocompatibility complex for maintenance, and directly correlated with the strength of T cell receptor (TCR) stimulus. Thus, our results define a novel tool for studying antigen receptor activation in vivo. Using this model, we show that regulatory T cells (T(reg) cells) and invariant NKT cells (iNKT cells) perceived stronger TCR signals than conventional T cells during development. However, although T(reg) cells continued to perceive strong TCR signals in the periphery, iNKT cells did not. Finally, we show that T(reg) cell progenitors compete for recognition of rare stimulatory TCR self-ligands.

Pubmed ID: 21606508

Authors

  • Moran AE
  • Holzapfel KL
  • Xing Y
  • Cunningham NR
  • Maltzman JS
  • Punt J
  • Hogquist KA

Journal

The Journal of experimental medicine

Publication Data

June 6, 2011

Associated Grants

  • Agency: NIAID NIH HHS, Id: P01 AI035296
  • Agency: NIAID NIH HHS, Id: R01 AI039560
  • Agency: NIAID NIH HHS, Id: R01 AI39560
  • Agency: NIAID NIH HHS, Id: R37 AI039560
  • Agency: NIAID NIH HHS, Id: T32 AI007313

Mesh Terms

  • Animals
  • Bone Marrow Cells
  • Chromosomes, Artificial, Bacterial
  • Flow Cytometry
  • Fluorescent Dyes
  • Genes, Reporter
  • Green Fluorescent Proteins
  • Inflammation
  • Ligands
  • Mice
  • Mice, Transgenic
  • Natural Killer T-Cells
  • Receptors, Antigen, T-Cell
  • T-Lymphocytes, Regulatory
  • Thymus Gland
  • Up-Regulation