Role of LAG-3 in Regulatory T Cells
Open accessAbstract
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.
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Dysfunctional T cells express, to different degrees, inhibitory molecules including PD-1, Tim-3, LAG-3, 2B4, CD160, and KLRG-1.
“compelling evidence indicate that dysfunctional T cells express in different degrees the “inhibitory” molecules including PD-1, Tim-3, LAG-3, 2B4, CD160, and KLGR-1.”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [75]
Different categories of T cell abnormalities may be mechanistically intertwined.
“It suggests that different categories of T cell abnormalities may be mechanistically intertwined [28,74–76].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [75]
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- Authors
- 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.
- Affiliations
- Johns Hopkins University (US)
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Drake, Charles G.
- Vignali, Dario A.A.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2004-10
- Volume
- 21
- Issue
- 4
- Pages
- 503-513
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1988474688
- Cited by
- 1,325
- References
- 3
- Citations by year
- 2026: 39 · 2025: 57 · 2024: 98 · 2023: 84 · 2022: 79 · 2021: 115 · 2020: 77 · 2019: 103 · 2018: 64 · 2017: 75 · 2016: 72 · 2015: 57 · 2014: 40 · 2013: 40 · 2012: 46
- FWCI
- 14.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA21765, P30CA021765)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- LAG-3, regulatory T cells, immunosuppression, MHC class II binding, CD4+CD25+ T cells, Treg differentiation, autoimmunity, antitumor immunity
- MeSH terms
- Lymphocyte Activation Gene 3 Protein, Animals, Cell Differentiation, Hemagglutinins, Immune Tolerance, Immunohistochemistry, Immunologic Memory, Lung Diseases, Mice, Transgenic, Receptors, Antigen, T-Cell, T-Lymphocytes, Transduction, Genetic, Vasculitis, Receptors, Interleukin-2, Biomarkers, Antigens, CD, CD4 Antigens, Adoptive Transfer, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice
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