Lymphocyte activation gene-3 (CD223) regulates the size of the expanding T cell population following antigen activation in vivo

J Immunol. 2004 May 1;172(9):5450-5. doi: 10.4049/jimmunol.172.9.5450.


Lymphocyte activation gene-3 (LAG-3) is a CD4-related, activation-induced cell surface molecule that binds to MHC class II with high affinity. In this study, we used four experimental systems to reevaluate previous suggestions that LAG-3(-/-) mice had no T cell defect. First, LAG-3(-/-) T cells exhibited a delay in cell cycle arrest following in vivo stimulation with the superantigen staphylococcal enterotoxin B resulting in increased T cell expansion and splenomegaly. Second, increased T cell expansion was also observed in adoptive recipients of LAG-3(-/-) OT-II TCR transgenic T cells following in vivo Ag stimulation. Third, infection of LAG-3(-/-) mice with Sendai virus resulted in increased numbers of memory CD4(+) and CD8(+) T cells. Fourth, CD4(+) T cells exhibited a delayed expansion in LAG-3(-/-) mice infected with murine gammaherpesvirus. In summary, these data suggest that LAG-3 negatively regulates T cell expansion and controls the size of the memory T cell pool.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Bacterial / pharmacology*
  • Antigens, CD / genetics
  • Antigens, CD / physiology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Division
  • Enterotoxins / pharmacology*
  • Gammaherpesvirinae / immunology
  • Herpesviridae Infections / genetics
  • Herpesviridae Infections / immunology
  • Immunologic Memory / genetics
  • Lymphocyte Activation*
  • Lymphocyte Count
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Respirovirus Infections / genetics
  • Respirovirus Infections / immunology
  • Sendai virus / immunology
  • Splenomegaly / genetics
  • Splenomegaly / immunology
  • Staphylococcus aureus / immunology
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocyte Subsets / transplantation


  • Antigens, Bacterial
  • Antigens, CD
  • CD223 antigen
  • Enterotoxins
  • Receptors, Antigen, T-Cell, alpha-beta
  • enterotoxin B, staphylococcal