Soluble human lymphocyte activation gene-3 modulates allospecific T cell responses

International Immunology
M SubramanyamM A Tepper

Abstract

Lymphocyte activation gene (LAG)-3, a member of the Ig superfamily, has been characterized as an activation antigen of T cells and NK cells. LAG-3 has been proposed as an alternate ligand for HLA class II due to some sequence homology and similarities in exon-intron organization with CD4. Here, we report the functional evaluation of a soluble Ig fusion molecule of human LAG-3 (LAG-3-Ig) in T cell activation assays. Cytofluorimetry studies revealed LAG-3-Ig binding predominantly to class II-expressing cells. In functional assays, inhibition of primary allogeneic mixed lymphocyte response (MLR) and murine-human xenogeneic MLR was observed in the presence of LAG-3-Ig. Effects of LAG-3-Ig addition were not observed on mitogen-, recall antigen- or superantigen-mediated stimulation. Cytotoxic T lymphocyte effector functions were also not affected by LAG-3-Ig. Inhibition of alloresponses by LAG-3-Ig occurred within the first 24 h of activation, resulting in a strong inhibition of IL-2 production. Unlike blockade of the CD28 receptor, however, LAG-3-Ig-mediated inhibition could not be reversed by exogenous IL-2 supplementation. Cytofluorimetric analysis of the phenotype of cells exposed to LAG-3-Ig in MLR cultures revealed a decrease i...Continue Reading

Citations

Feb 22, 2005·Immunology·Sandrine Buisson, Frédéric Triebel
Jan 6, 2021·Current Atherosclerosis Reports·Annabelle Rodriguez

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