Innate-like T cells straddle innate and adaptive immunity by altering antigen-receptor responsiveness

Nat Immunol. 2014 Jan;15(1):80-7. doi: 10.1038/ni.2773. Epub 2013 Nov 17.


The subclassification of immunology into innate and adaptive immunity is challenged by innate-like T lymphocytes that use innate receptors to respond rapidly to stress despite expressing T cell antigen receptors (TCRs), a hallmark of adaptive immunity. In studies that explain how such cells can straddle innate and adaptive immunity, we found that signaling via antigen receptors, whose conventional role is to facilitate clonal T cell activation, was critical for the development of innate-like T cells but then was rapidly attenuated, which accommodated the cells' innate responsiveness. These findings permitted the identification of a previously unknown innate-like T cell subset and indicate that T cell hyporesponsiveness, a state traditionally linked to tolerance, may be fundamental to T cells entering the innate compartment and thereby providing lymphoid stress surveillance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology*
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Flow Cytometry
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Immunity, Innate / immunology*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / immunology
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • ZAP-70 Protein-Tyrosine Kinase / immunology
  • ZAP-70 Protein-Tyrosine Kinase / metabolism


  • Interleukin-17
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, gamma-delta
  • Green Fluorescent Proteins
  • ZAP-70 Protein-Tyrosine Kinase
  • Zap70 protein, mouse