A novel regulatory role of gp49B on dendritic cells in T-cell priming
A novel regulatory role of gp49B on dendritic cells in T-cell priming
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DOI：
10.1002/eji.200737550
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发表时间：
2008-09-01
影响因子：
5.4
通讯作者：
Takai, Toshiyuki
中科院分区：
文献类型：
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作者：
Kasai, Satoshi;Inui, Masanori;Takai, Toshiyuki
树突状细胞（DC）在先天免疫和获得性免疫的诱导和调节中起着关键作用。DC表达多种细胞表面免疫抑制受体。然而，在t细胞活化的背景下，它们潜在的免疫调节功能知之甚少。在这里，我们报道了小鼠gp49B，免疫球蛋白超家族的一员，含有免疫受体酪氨酸抑制基序，在DC上表达并下调细胞活性，以防止体外和体内T细胞的过度激活。与野生型小鼠骨髓源性DC相比，新生成的gp49B缺陷（gp49B(-/-)）小鼠骨髓源性DC （BMDC）以细胞-细胞接触的方式诱导抗原特异性CD4（+）和CD8(+) T细胞的增殖和IL-2释放增强。qp49B(-/-) BMDC对同种异体CD4（+）和CD8(+) T细胞的增殖也有促进作用。此外，将同种异体BALB/c脾细胞转移到C57BL/6 gp49B（-/-）小鼠体内可诱导严重的急性移植物抗宿主病，并伴有CD86对CD11c（+）脾gp49B(-/-) DC的增强上调，而将C57BL/6 gp49B（-/-）脾细胞转移到BALB/c小鼠体内则不会，这表明疾病的恶化至少部分是由于受体gp49B-/- DC的增强活化。这些发现证明了gp49B在DC功能中的一种新的调节作用。
Dendritic cells (DC) play pivotal roles in the induction and regulation of both innate and acquired immunity. DC express several cell-surface immune inhibitory receptors. However, little is known about their potential immunoregulatory functions in the context of T-cell activation. Here we report that murine gp49B, a member of the immunoglobulin superfamily, harboring immunoreceptor tyrosine-based inhibitory motifs, is expressed on DC and downregulates cellular activity to prevent the excessive activation of T cells in vitro and in vivo. Bone marrow-derived DC (BMDC) from newly generated gp49B-deficient (gp49B(-/-)) mice induced enhanced proliferation and IL-2 release of antigen-specific CD4(+) and CD8(+) T cells compared with BMDC from wild-type mice, in a cell-cell contact manner. The enhanced proliferation by qp49B(-/-) BMDC was also observed in allogeneic CD4(+) and CD8(+) T cells. Moreover, the transfer of allogeneic BALB/c splenocytes into C57BL/6 gp49B(-/-) mice induced severe acute graft-versus-host disease with an augmented upregulation of CD86 on CD11c(+) splenic gp49B(-/-) DC, while transfer of C57BL/6 gp49B(-/-) splenocytes into BALB/c mice did not, suggesting the exacerbation of the disease was due, at least in part, to augmented activation of recipient gp49B-/- DC. These findings demonstrate a novel regulatory role of gp49B in the function of DC.