Exacerbated graft-versus-host disease in Pirb-/- mice
Exacerbated graft-versus-host disease in Pirb-/- mice
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DOI：
10.1038/ni1074
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发表时间：
2004-06-01
影响因子：
30.5
通讯作者：
Takai, T
中科院分区：
文献类型：
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作者：
Nakamura, A;Kobayashi, E;Takai, T
免疫反应通常由识别相同配体但传递激活或抑制信号的相反受体对调节。在B细胞和骨髓细胞上表达的成对免疫球蛋白样受体（PIR）包含调节这些细胞的反应性的主要组织相容性复合物I类识别系统。在这里，激活PIR-A和抑制PIR-B结合各种小鼠主要组织相容性复合物I类（H-2）分子，并在体外H-2四聚体刺激B细胞上的PIR-B或巨噬细胞上的PIR-A诱导细胞内磷酸酪氨酸信号传导。在将同种异体脾细胞转移到PIR-B缺陷小鼠中后，小鼠显示出恶化的移植物抗宿主病，这是由于受体树突状细胞的活化增强以及伴随的PIR-A上调和干扰素γ产生增加。PIR-A诱导的树突状细胞活化也导致供体细胞毒性T细胞增殖增加。因此，PIR-A和PIR-B是成功的组织移植所必需的抵消受体，并且可以在生理条件下以组成性方式调节对自体组织的不相关反应。
Immune responses are often regulated by opposing receptor pairs that recognize the same ligand but deliver either activating or inhibitory signals. Paired immunoglobulin-like receptors (PIRs) expressed on B cells and myeloid cells comprise a major histocompatibility complex class I recognition system that regulates the responsiveness of these cells. Here, activating PIR-A and inhibitory PIR-B bound various mouse major histocompatibility complex class I (H-2) molecules, and in vitro H-2 tetramer stimulation of PIR-B on B cells or PIR-A on macrophages induced intracellular phosphotyrosine signaling. After transfer of allogeneic splenocytes into PIR-B-deficient mice, the mice showed exacerbated graft-versus-host disease, which was due to augmented activation of recipient dendritic cells with concomitant upregulation of PIR-A and increased interferongamma-production. PIR-A-induced dendritic cell activation also led to increased proliferation of donor cytotoxic T cells. Thus, PIR-A and PIR-B are counteracting receptors that are essential for successful tissue transplantation and may regulate irrelevant reaction to autologous tissues in a constitutive way in physiological conditions.