Proliferation of activated CD1d-restricted NKT cells is down-modulated by lymphocyte activation gene-3 signaling via cell cycle arrest in S phase

Cell Biol Int. 2007 Mar;31(3):257-62. doi: 10.1016/j.cellbi.2006.11.002. Epub 2006 Nov 14.


Upon antigenic stimulation, CD1d-restricted NKT cells quickly secrete large amounts of cytokines. This prompt response demonstrates that CD1d-restricted NKT cells may potentially prove to be useful therapeutic agents for the treatment of many diseases. Despite the clinical importance of CD1d-restricted NKT cells, the regulating mechanisms of this unique T cell population remain to be defined. We found murine LAG-3 is inducible on CD1d-restricted NKT cells as the result of a variety of stimulants such as concanavalin A (con A) and anti-CD3. Also, antigen-specific CD1d stimulation can elicit LAG-3 in CD1d-restricted NKT cells. Moreover, ectopic LAG-3 expression on CD1d-restricted NKT cells results in cell cycle arrest in the S phase. These results show that LAG-3 signaling on activated CD1d-restricted NKT cells may down-modulate NKT cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology*
  • Antigens, CD1 / immunology*
  • Cell Proliferation
  • Down-Regulation
  • Gene Expression Regulation / immunology*
  • Immunologic Factors
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / genetics*
  • Mice
  • S Phase / genetics
  • Signal Transduction / immunology*
  • Transduction, Genetic


  • Antigens, CD
  • Antigens, CD1
  • CD223 antigen
  • Immunologic Factors