Liver sinusoidal endothelial cells that endocytose allogeneic cells suppress T cells with indirect allospecificity
Liver sinusoidal endothelial cells that endocytose allogeneic cells suppress T cells with indirect allospecificity
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DOI：
10.4049/jimmunol.177.6.3615
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发表时间：
2006-09-15
影响因子：
4.4
通讯作者：
Asahara, Toshimasa
中科院分区：
文献类型：
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作者：
Tokita, Daisuke;Shishida, Masayuki;Asahara, Toshimasa
已知门静脉注射同种异体供体细胞可延长随后移植的同种异体移植物的存活。在这项研究中，我们研究了肝窦内皮细胞（LSECs）在门静脉注射同种异体细胞对间接同种异体特异性T细胞诱导的免疫抑制作用中的作用。为了消除直接的CD 4 + T细胞应答，使用C57 BL/6（B6）MHC II类缺陷型C2 ta（tm 1Ccum）（C2 D）小鼠作为供体。照射B6 C2 D脾细胞门静脉注射到BALB/c小鼠后，宿主LSEC内吞照射同种异体脾细胞表现出增强的MHC II类分子，CD 80和Fas配体（FasL）的表达。由于经门静脉注射B6 C2 D脾细胞处理的BALB/c小鼠穿过LSEC的迁移，初始BALB/c CD 4（+）T细胞失去了对内吞供体型B6 C2 D同种异体抗原的BALB/c脾APC的刺激的反应性，同时保持对内吞第三方C3 H同种异体抗原的BALB/c脾APC的刺激的正常反应。对于经门静脉注射B6 C2 D脾细胞处理的BALB/c FasL缺陷小鼠，未处理的BALB/c CD 4（+）T细胞穿过LSEC时未观察到类似的结果。通过门静脉将内吞B6 C2 D脾细胞的BALB/c LSEC适应性转移到BALB/c小鼠中延长了随后移植的B6 C2 D心脏的存活时间;然而，在BALB/c FasL缺陷的LSEC中未观察到类似的效果。这些发现表明，具有内吞的同种异体脾细胞的LSEC对具有间接同种特异性的T细胞具有免疫抑制作用，至少部分地通过Fas/FasL途径。
A portal venous injection of allogeneic donor cells is known to prolong the survival of subsequently transplanted allografts. In this study, we investigated the role of liver sinusoidal endothelial cells (LSECs) in immunosuppressive effects induced by a portal injection of allogeneic cells on T cells with indirect allospecificity. To eliminate the direct CD4+ T cell response, C57BL/6 (B6) MHC class II-deficient C2ta(tm1Ccum) (C2D) mice were used as donors. After portal injection of irradiated B6 C2D splenocytes into BALB/c mice, the host LSECs that endocytosed the irradiated allogeneic splenocytes showed enhanced expression of MHC class II molecules, CD80, and Fas ligand (FasL). Due to transmigration across the LSECs from BALB/c mice treated with a portal injection of B6 C2D splenocytes, the naive BALB/c CD4(+) T cells lost their responsiveness to stimulus of BALB/c splenic APCs that endocytose donor-type B6 C2D alloantigens, while maintaining a normal response to stimulus of BALB/c splenic APCs that endocytose third-party C3H alloantigens. Similar results were not observed for naive BALB/c CD4(+) T cells that transmigrated across the LSECs from BALB/c FasL-deficient mice treated with a portal injection of B6 C2D splenocytes. Adaptive transfer of BALB/c LSECs that had endocytosed B6 C2D splenocytes into BALB/c mice via the portal vein prolonged the survival of subsequently transplanted B6 C2D hearts; however, a similar effect was not observed for BALB/c FasL-deficient LSECs. These findings indicate that LSECs that had endocytosed allogeneic splenocytes have immunosuppressive effects on T cells with indirect allospecificity, at least partially via the Fas/FasL pathway.