The CD4‐related molecule, LAG‐3 (CD223), regulates the expansion of activated T cells

CJ Workman, DAA Vignali - European journal of immunology, 2003 - Wiley Online Library
CJ Workman, DAA Vignali
European journal of immunology, 2003Wiley Online Library
The lymphocyte activation gene‐3 (LAG‐3, CD223) is a CD4‐related, activation‐induced
cell surface molecule that binds to MHC class II with high affinity. The function of murine LAG‐
3 on T cells is unclear. Here, we show that Vβ7/8+ LAG‐3–/–T cells expand poorly following
staphylococcal enterotoxin B (SEB) stimulation in vitro. LAG‐3–/–T cells proliferate at a
normal rate, but exhibit increased cell death. Similar observations were made with LAG‐3–/–
CD4+ OT‐II TCR transgenic T cells following peptide stimulation. Despite reduced T cell …
Abstract
The lymphocyte activation gene‐3 (LAG‐3, CD223) is a CD4‐related, activation‐induced cell surface molecule that binds to MHC class II with high affinity. The function of murine LAG‐3 on T cells is unclear. Here, we show that Vβ7/8+LAG‐3–/– T cells expand poorly following staphylococcal enterotoxin B (SEB) stimulation in vitro. LAG‐3–/– T cells proliferate at a normal rate, but exhibit increased cell death. Similar observations were made with LAG‐3–/–CD4+OT‐II TCR transgenic T cells following peptide stimulation. Despite reduced T cell expansion and increased cell death, LAG‐3–/–OT‐II+ T cells secrete more IL‐2 and IFN‐γ following stimulation. Antigen‐driven expansion of LAG‐3–/– T cells was restored by constitutive expression of LAG‐3 via retroviral‐mediated stem cell gene transfer. We further show that LAG‐3 function is mediated via its cytoplasmic domain, for which a conserved ‘KIEELE’ motif is essential. Our data support a role for LAG‐3 in regulating the expansion of activated T cells.
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