Cutting edge: Programmed death-1/programmed death ligand 1 interaction regulates the induction and maintenance of invariant NKT cell anergy

J Immunol. 2008 Nov 15;181(10):6707-10. doi: 10.4049/jimmunol.181.10.6707.


Invariant NKT (iNKT) cells are a distinct subset of T lymphocytes that recognize glycolipid Ags. Upon TCR stimulation, iNKT cells promptly secrete a wide range of cytokines and therefore have been investigated as a target for immunotherapy. However, after primary activation, iNKT cells become hyporesponsive toward their ligand (anergy). The further mechanism behind iNKT cell anergy is poorly understood. We found that a low level of programmed death-1 (PD-1) was constitutively expressed on iNKT cells and that PD-1 expression was increased after stimulation and lasted at least 2 mo. Moreover, not only did blocking of the PD-1/PD ligand 1 (PD-L1) pathway prevent the induction of anergy in iNKT cells, but anergic iNKT cells also recovered responsiveness and these "rescued" cells efficiently mediated antitumor immunity. Our findings suggest that the PD-1/PD-L1 interaction is essential for the induction and maintenance of iNKT cell anergy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / immunology*
  • Apoptosis Regulatory Proteins / immunology*
  • B7-1 Antigen / immunology*
  • B7-H1 Antigen
  • Clonal Anergy / immunology*
  • Cytotoxicity, Immunologic
  • Female
  • Flow Cytometry
  • Galactosylceramides / immunology
  • Lymphocyte Activation / immunology*
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Peptides / immunology*
  • Programmed Cell Death 1 Receptor
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / immunology*


  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Galactosylceramides
  • Membrane Glycoproteins
  • Pdcd1 protein, mouse
  • Peptides
  • Programmed Cell Death 1 Receptor
  • alpha-galactosylceramide