Lymphocyte activation gene-3 (CD223) regulates the size of the expanding T cell population following antigen activation in vivo.
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.
Workman
Creg J
CJ
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Cauley
Linda S
LS
Kim
In-Jeong
IJ
Blackman
Marcia A
MA
Woodland
David L
DL
Vignali
Dario A A
DA
D019264:Adoptive Transfer; D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division; D004768:Enterotoxins / Q000494:pharmacology*; D018142:Gammaherpesvirinae / Q000276:immunology; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D010253:Respirovirus Infections / Q000235:genetics / Q000276:immunology; D029082:Sendai virus / Q000276:immunology; D013163:Splenomegaly / Q000235:genetics / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D000093322:Lymphocyte Activation Gene 3 Protein
D000942:Antigens, Bacterial; D015703:Antigens, CD; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C031818:enterotoxin B, staphylococcal; D000093322:Lymphocyte Activation Gene 3 Protein