Role of LAG-3 in regulatory T cells.
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.
Huang
Ching-Tai
CT
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Workman
Creg J
CJ
Flies
Dallas
D
Pan
Xiaoyu
X
Marson
Aimee L
AL
Zhou
Gang
G
Hipkiss
Edward L
EL
Ravi
Sowmya
S
Kowalski
Jeanne
J
Levitsky
Hyam I
HI
Powell
Jonathan D
JD
Pardoll
Drew M
DM
Drake
Charles G
CG
Vignali
Dario A A
DA
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis*; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D020869:Gene Expression Profiling; D006388:Hemagglutinins / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D007150:Immunohistochemistry; D007156:Immunologic Memory; D008171:Lung Diseases / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic; D014657:Vasculitis / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; D015415:Biomarkers; D015704:CD4 Antigens; D006388:Hemagglutinins; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse