T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses
T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses
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DOI：
10.1073/pnas.1107087108
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发表时间：
2011-11-22
影响因子：
11.1
通讯作者：
Rouse, Barry T.
中科院分区：
文献类型：
--
作者：
Sharma, Shalini;Sundararajan, Aarthi;Rouse, Barry T.
对病原体的反应通常会影响免疫并限制组织损伤。几种宿主抗炎机制抑制组织损伤，但这些也可能限制对急性感染的免疫效果，正如我们在急性感染甲型流感病毒（IAV）的小鼠中所证明的那样。我们发现，与野生型（WT）相比，半乳糖凝集素-9敲除（G9KO）小鼠表现出更强的急性期病毒特异性CD8 t细胞反应，以及更高和更快的病毒特异性血清IgM、IgG和IgA反应，并且比野生型小鼠更快地清除病毒。使用Tim-3融合蛋白阻断半乳糖凝集素-9信号到表达Tim-3的细胞可改善WT小鼠的免疫反应。当IAV免疫小鼠被异源IAV攻击时，G9KO中继发性IAV特异性CD8 t细胞反应比WT小鼠高4 - 5倍。我们的研究结果表明，操纵凝集素信号可能是一种改善对某些疫苗免疫反应的便捷方法。
Reactions to pathogens are usually tuned to effect immunity and limit tissue damage. Several host counterinflammatory mechanisms inhibit tissue damage but these may also act to constrain the effectiveness of immunity to acute infections, as we demonstrate in mice acutely infected with influenza A virus (IAV). We show that compared with wild type (WT), galectin-9 knockout (G9KO) mice mounted a more robust acute phase virus-specific CD8 T-cell response as well as higher and more rapid virus-specific serum IgM, IgG, and IgA responses and also cleared virus more rapidly than did WT mice. Blocking galectin-9 signals to Tim-3-expressing cells using a Tim-3 fusion protein resulted in improved immune responses in WT mice. When IAV immune mice were challenged with a heterologous IAV, the secondary IAV-specific CD8 T-cell responses were four-to fivefold higher in G9KO compared with WT mice. Our results indicate that manipulating galectin signals may represent a convenient approach to improve immune responses to some vaccines.