Rapid dendritic cell activation and resistance to allotolerance induction in anti-CD154-treated mice receiving CD47-deficient donor-specific transfusion.
Rapid dendritic cell activation and resistance to allotolerance induction in anti-CD154-treated mice receiving CD47-deficient donor-specific transfusion.
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接受 CD47 缺陷供体特异性输血的抗 CD154 治疗小鼠的快速树突状细胞激活和对同种异体耐受诱导的抵抗
DOI：
10.3727/096368912x661346
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发表时间：
2014-03
影响因子：
3.3
通讯作者：
Yang YG
中科院分区：
文献类型：
--
作者：
Wang Y;Wang H;Bronson R;Fu Y;Yang YG
CD47Sirpα信号在调节巨噬细胞和树突状细胞(DC)活化中起重要作用。在此，我们研究了供者细胞上CD47的表达在供者特异性输血(DST)和抗CD154单抗联合治疗诱导MHC完全不相合的同种异体心脏移植耐受中的作用。大多数接受抗CD154和CD47+/+B6脾细胞(DST)的BALB/c受体小鼠表现出不确定的供心存活(中位存活时间，MST和GT；150D)。尽管供心存活率比未治疗组(mst=7d)和单独抗CD154dst组(mst=15d)有所改善，但接受CD47+/−(mst=90d)或CD47CD47B6dst(mst=42d)的抗CD154治疗的BALB/c小鼠的移植物存活时间比接受−/−+/+B6dst组显著缩短。与接受抗CD154和CD47+/+−/−的小鼠相比，接受抗CD154+CD47DST或CD47+/DST治疗的受体小鼠的抗供体−反应显著增加，但不抗第三方MLR反应。此外，CD47−/−DST通过不依赖供体同种异体抗原的机制诱导CD11chiSIRPαhiCD8α−DC的快速激活。这些结果表明，供者细胞表面CD47的表达是联合应用DST和CD40/CD154阻断诱导耐受成功的关键。
CD47-SIRPα signaling plays an important role in regulating macrophage and dendritic cell (DC) activation. Here, we investigated the role of CD47 expression on donor cells in tolerance induction by combined treatment with donor-specific transfusion (DST) plus anti-CD154 mAb in a mouse model of fully MHC-mismatched heart allotransplantation. The majority of BALB/c recipient mice that received anti-CD154 and CD47+/+ B6 splenocytes (DST) showed indefinite donor heart survival (median survival time, MST>150d). Although donor heart survival was improved compared to non-treated (MST=7d) and anti-CD154 alone (MST=15d) controls, the graft survival time was significantly reduced in anti-CD154-treated BALB/c mice that received CD47+/− (MST=90d) or CD47−/− B6 DST (MST=42d) compared to those receiving CD47+/+ B6 DST. Recipient mice treated with anti-CD154 plus CD47−/− or CD47+/− DST also showed significantly increased anti-donor, but not anti-3rd-party, MLR responses compared to those receiving anti-CD154 and CD47+/+ DST. Furthermore, CD47−/− DST induced rapid activation of CD11chiSIRPαhiCD8α− DCs via a mechanism independent of donor alloantigens. These results demonstrate that CD47 expression on donor cells is essential to the success of tolerance induction by combined therapy with DST and CD40/CD154 blockade.