Galectin-9 binding to Tim-3 renders activated human CD4+ T cells less susceptible to HIV-1 infection
Galectin-9 binding to Tim-3 renders activated human CD4+ T cells less susceptible to HIV-1 infection
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DOI：
10.1182/blood-2011-11-389585
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发表时间：
2012-05-03
期刊：
影响因子：
20.3
通讯作者：
Horton, Helen
中科院分区：
文献类型：
--
作者：
Elahi, Shokrollah;Niki, Toshiro;Horton, Helen
Galectin-9(Galectin-9，Galectin-9)是Galectin家族的串联重复型成员，是T细胞免疫球蛋白粘蛋白结构域3(TIM-3)的配基，TIM-3是一种I型糖蛋白，在慢性感染时持续表达在功能障碍的T细胞上。对自身免疫性疾病和慢性病毒感染的研究表明，TIM-3是一种抑制Th1型免疫反应的调节分子。在这里，我们显示了可溶性的Gal-9与表达在激活的CD4(+)T细胞表面的TIM-3相互作用，使它们不太容易感染和复制HIV-1。Gal-9/Tim-3与活化的CD4(+)T细胞相互作用，导致HIV-1辅受体下调和细胞周期蛋白依赖性激酶抑制因子p21(也称为CIP-1和WAF-1)上调。我们认为，在慢性感染期间，TIM-3的高表达已经进化为限制持续免疫激活和相关的组织损伤。这些结果证明了Gal-9/Tim-3相互作用诱导活化的CD4(+)T细胞对HIV-1感染产生抵抗力的新机制，并提示Gal-9可能在HIV-1的发病机制中发挥作用，并可能作为一种新型的杀菌剂用于预防HIV-1感染。(血。2012年；119(18)：4192-4204)
Galectin-9 (Gal-9) is a tandem repeat-type member of the galectin family and is a ligand for T-cell immunoglobulin mucin domain 3 (Tim-3), a type-I glycoprotein that is persistently expressed on dysfunctional T cells during chronic infection. Studies in autoimmune diseases and chronic viral infections show that Tim-3 is a regulatory molecule that inhibits Th1 type immune responses. Here we show that soluble Gal-9 interacts with Tim-3 expressed on the surface of activated CD4(+) T cells and renders them less susceptible to HIV-1 infection and replication. The Gal-9/Tim-3 interaction on activated CD4(+) T cells, leads to down-regulation of HIV-1 coreceptors and up-regulation of the cyclin-dependent kinase inhibitor p21 (also known as cip-1 and waf-1). We suggest that higher expression of Tim-3 during chronic infection has evolved to limit persistent immune activation and associated tissue damage. These data demonstrate a novel mechanism for Gal-9/Tim-3 interactions to induce resistance of activated CD4(+) T cells to HIV-1 infection and suggest that Gal-9 may play a role in HIV-1 pathogenesis and could be used as a novel microbicide to prevent HIV-1 infection. (Blood. 2012;119(18):4192-4204)