Role of LAG-3 in regulatory T cells

Ching Tai Huang, Creg J. Workman, Dallas Flies, Xiaoyu Pan, Aimee L. Marson, Gang Zhou, Edward L. Hipkiss, Sowmya Ravi, Jeanne Kowalski, Hyam I. Levitsky, Jonathan D. Powell, Drew M. Pardoll, Charles G. Drake, Dario A.A. Vignali

Research output: Contribution to journalArticle

643 Scopus citations

Abstract

Regulatory T cells (Tregs) limit autoimmunity but also attenuate the magnitude of antipathogen and antitumor immunity. Understanding the mechanism of Treg function and therapeutic manipulation of Tregs in vivo requires identification of Treg-selective receptors. A comparative analysis of gene expression arrays from antigen-specific CD4+ T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg-selective expression of LAG-3, a CD4-related molecule that binds MHC class II. Antibodies to LAG-3 inhibit suppression by induced Tregs both in vitro and in vivo. Natural CD4+CD25+ Tregs express LAG-3 upon activation, which is significantly enhanced in the presence of effector cells, whereas CD4 +CD25+ Tregs from LAG-3-/- mice exhibit reduced regulatory activity. Lastly, ectopic expression of LAG-3 on CD4+ T cells significantly reduces their proliferative capacity and confers on them suppressor activity toward effector T cells. We propose that LAG-3 marks regulatory T cell populations and contributes to their suppressor activity.

Original languageEnglish (US)
Pages (from-to)503-513
Number of pages11
JournalImmunity
Volume21
Issue number4
DOIs
StatePublished - Oct 1 2004

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Huang, C. T., Workman, C. J., Flies, D., Pan, X., Marson, A. L., Zhou, G., Hipkiss, E. L., Ravi, S., Kowalski, J., Levitsky, H. I., Powell, J. D., Pardoll, D. M., Drake, C. G., & Vignali, D. A. A. (2004). Role of LAG-3 in regulatory T cells. Immunity, 21(4), 503-513. https://doi.org/10.1016/j.immuni.2004.08.010