Avice M N, Sarfati M, Triebel F, Delespesse G, Demeure C E
Laboratoire de Recherche sur l'Allergie, Université de Montréal, Centre de Recherche Louis-Charles Simard, Montréal, Québec, Canada.
J Immunol. 1999 Mar 1;162(5):2748-53.
Lymphocyte activation gene-3 (LAG-3) is an MHC class II ligand structurally and genetically related to CD4. Although its expression is restricted to activated T cells and NK cells, the functions of LAG-3 remain to be elucidated. Here, we report on the expression and function of LAG-3 on proinflammatory bystander T cells that are activated in the absence of TCR engagement. LAG-3 is expressed at high levels on human T cells cocultured with autologous monocytes and IL-2 and synergizes with the low levels of CD40 ligand (CD40L) expressed on these cells to trigger TNF-alpha and IL-12 production by monocytes. Indeed, anti-LAG-3 mAb inhibits both IL-12 and IFN-gamma production in IL-2-stimulated cocultures of T cells and autologous monocytes. Soluble LAG-3Ig fusion protein markedly enhances IL-12 production by monocytes stimulated with infra-optimal concentrations of sCD40L, whereas it directly stimulates monocyte-derived dendritic cells (DC) for the production of TNF-alpha and IL-12, unravelling an enhanced responsiveness to MHC class II engagemenent in DC as compared with activated monocytes. Thus similar to CD40L, LAG-3 may be involved in the proinflammatory activity of cytokine-activated bystander T cells and most importantly it may directly activate DC.
淋巴细胞激活基因-3（LAG-3）是一种在结构和基因上与CD4相关的MHC II类配体。尽管其表达仅限于活化的T细胞和NK细胞，但LAG-3的功能仍有待阐明。在此，我们报告了LAG-3在未通过TCR参与而被激活的促炎性旁观者T细胞上的表达和功能。LAG-3在与自体单核细胞和IL-2共培养的人T细胞上高水平表达，并与这些细胞上低水平表达的CD40配体（CD40L）协同作用，以触发单核细胞产生TNF-α和IL-12。实际上，抗LAG-3单克隆抗体抑制T细胞和自体单核细胞的IL-2刺激共培养物中IL-12和IFN-γ的产生。可溶性LAG-3Ig融合蛋白显著增强用次优浓度的sCD40L刺激的单核细胞产生IL-12，而它直接刺激单核细胞衍生的树突状细胞（DC）产生TNF-α和IL-12，揭示了与活化的单核细胞相比，DC对MHC II类参与的反应性增强。因此，与CD40L相似，LAG-3可能参与细胞因子激活的旁观者T细胞的促炎活性，最重要的是它可能直接激活DC。
