Induction of Specific Tolerance by Hepatic Double-Negative CD4-8-αβ T Cells of Mice Immunized with Allogeneic Cells via the Portal Vein in Vitro
Induction of Specific Tolerance by Hepatic Double-Negative CD4-8-αβ T Cells of Mice Immunized with Allogeneic Cells via the Portal Vein in Vitro
复制标题
异体细胞门静脉免疫小鼠肝脏双阴性CD4-8-αβ T细胞体外诱导特异性耐受
DOI：
10.1006/cimm.1993.1140
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发表时间：
1993
影响因子：
4.3
通讯作者：
K. Kumagai
中科院分区：
文献类型：
--
作者：
N. Koyamada;T. Ohteki;T. Abo;T. Fukumori;N. Ohkouchi;S. Satomi;Y. Taguchi;A. Kusumi;S. Mori;K. Kumagai
本研究通过门静脉途径免疫BALB/c（H-2d）小鼠AKR/n（H-2k）脾细胞，观察肝单个核细胞（MNC）在同种抗原特异性免疫耐受诱导中的作用。经证明，PV给药小鼠肝脏和脾脏中的MNC可消除同种异体MLR中对AKR/n同种抗原的反应。相反，在肝脏和脾脏的MNC皮下注射相同的抗原的小鼠表现出更大的反应比对照组小鼠。PV给药诱导的耐受是同种抗原特异性的，并且在肝MNC中比脾MNC中出现得更早。此外，当这些细胞加入到同种异体MLR中时，PV给药小鼠的肝MNC具有抑制作用，其中丝裂霉素C（MMC）处理的AKR/n脾MNC用作刺激物，对照BALB/c脾MNC用作应答物。PV给药小鼠的脾MNC和对照小鼠的肝MNC未显示出这种抑制作用。这种抑制是同种抗原特异性的，因为当将PV给药小鼠的肝脏MNC加入到使用MMC处理的C57 BL/6（H-2 B）脾脏MNC的系统中时，未诱导抑制。肝MNC诱导的同种抗原特异性抑制可通过去除TcR-αβ +细胞而消除，但不能去除肝MNC中的CD 4+、CD 8+和B220 +细胞。这些结果表明，同种抗原特异性抑制细胞主要出现在PV给药小鼠的肝脏MNC中，并显示TcR-αβ + CD 4 - 8 -双阴性T细胞的表型，尽管同种抗原特异性耐受在肝脏和脾脏MNC中均被诱导。
Abstract We immunized AKR/n (H-2 k ) spleen cells in BALB/c (H-2 d ) mice via the portal vein (pv) and investigated the role of hepatic mononuclear cells (MNC) in the induction of alloantigen-specific immune tolerance. MNC in the liver and spleen of pv-administered mice were demonstrated to abrogate the responses to AKR/n alloantigens in allogeneic MLR. On the contrary, MNC in the liver and spleen of mice administered subcutaneously with the same antigens showed greater responses than those of control mice. The tolerance induced by pv administration was alloantigen-specific and appeared earlier in hepatic MNC than in splenic MNC. Furthermore, hepatic MNC of pv-administered mice had a suppressive effect when these cells were added to allogeneic MLR, in which mitomycin C (MMC)-treated AKR/n splenic MNC were used as stimulator and control BALB/c splenic MNC were used as responder. Splenic MNC of pv-administered mice and hepatic MNC of control mice did not show such suppressive effects. Such suppression was alloantigen-specific, since no suppression was induced when hepatic MNC of pv-administered mice were added to a system using MMC-treated C57BL/6 (H-2 b ) splenic MNC. The alloantigen-specific suppression induced by hepatic MNC was abrogated by a depletion of TcR-αβ + cells but not of CD4 + , CD8 + , nor B220 + cells from hepatic MNC. These results suggested that alloantigen-specific suppressor cells appeared predominantly in the hepatic MNC of pv-administered mice and displayed the phenotype of TcR-αβ + CD4 - 8 - double-negative T cells, although alloantigen-specific tolerance was induced in both hepatic and splenic MNC.