Lymphocyte activation gene-3 (CD223) regulates the size of the expanding T cell population following antigen activation in vivo |
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Authors: | Workman Creg J Cauley Linda S Kim In-Jeong Blackman Marcia A Woodland David L Vignali Dario A A |
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Affiliation: | Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. |
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Abstract: | 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. |
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