Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80(dim), CD86(-)) prolong cardiac allograft survival in nonimmunosuppressed recipients
Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80(dim), CD86(-)) prolong cardiac allograft survival in nonimmunosuppressed recipients
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DOI：
10.1097/00007890-199609150-00021
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发表时间：
1996-09-15
期刊：
影响因子：
6.2
通讯作者：
Thomson, AW
中科院分区：
文献类型：
--
作者：
Fu, FM;Li, YP;Thomson, AW
我们以前已经表明，粒细胞-巨噬细胞集落刺激因子刺激的小鼠骨髓来源的MHC II类+树突状细胞（DC）祖细胞的细胞表面表达的共刺激分子B7-1（CD 80）和B7-2（CD 86）的缺陷，可以诱导同种异体抗原特异性T细胞在体外无能。为了测试这些发现的体内相关性，将体外诱导T细胞低反应性的2 × 10（6）B10（H2（B））小鼠骨髓来源的DC祖细胞（NLDC 145（+），MHC II类+，B7-1（dim）B7-2（-/dim））全身注射到正常C3 H（H2（k））受体中。7天后，小鼠接受来自B10供体的异位心脏移植，未给予免疫抑制剂治疗，移植物的中位存活时间从9.5天显著延长至22天，移植物的中位存活时间也有所增加，但程度较轻（16.5天），在接受第三方（BALB/c; H2（d））DC祖细胞，DC祖细胞注射后7天宿主T细胞对供体和第三方同种异体抗原的应答的离体分析（心脏移植时间）显示最小的抗供体混合白细胞反应和细胞毒性T淋巴细胞反应，与用“成熟"粒细胞-巨噬细胞集落刺激因子+白细胞介素-4-刺激的DC（MHC II类bright，B7-1（+），B7-2（bright）），其中许多以加速的方式排斥它们的心脏移植物。在迁移到受体次级淋巴组织的注射的供体MHC II类+ DC祖细胞中，有似乎具有上调的细胞表面B7-1和B7-2分子表达的细胞。这一观察结果可以解释，至少部分，在nonimmunosuppressed收件人的DC祖细胞诱导的低反应性的暂时或不稳定的性质。
We have shown previously that granulocyte-macrophage colony-stimulating factor-stimulated mouse bone marrow-derived MHC class II+ dendritic cell (DC) progenitors that are deficient in cell surface expression of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) can induce alloantigen-specific T-cell anergy in vitro. To test the in vivo relevance of these findings, 2 x 10(6) B10 (H2(b)) mouse bone marrow-derived DC progenitors (NLDC 145(+), MHC class II+, B7-1(dim) B7-2(-/dim)) that induced T-cell hyporesponsiveness in vitro were injected systemically into normal C3H (H2(k)) recipients. Seven days later, the mice received heterotopic heart transplants from B10 donors, No immunosuppressive treatment was given, Median graft survival time was prolonged significantly from 9.5 to 22 days, Median graft survival time was also increased, although to a lesser extent (16.5 days), in mice that received third-party (BALB/c; H2(d)) DC progenitors, Ex vivo analysis of host T-cell responses to donor and third-party alloantigens 7 days after the injection of DC progenitors (the time of heart transplant) revealed minimal anti-donor mixed leukocyte reaction and cytotoxic T lymphocyte reactivity, These responses were reduced substantially compared with those of spleen cells from animals pretreated with ''mature'' granulocyte-macrophage colony-stimulating factor + interleukin-4-stimulated DC (MHC class IIbright, B7-1(+), B7-2(bright)), many of which rejected their heart grafts in an accelerated fashion, Among the injected donor MHC class II+ DC progenitors that migrated to recipient secondary lymphoid tissue were cells that appeared to have up-regulated cell surface B7-1 and B7-2 molecule expression. This observation may explain, at least in part, the temporary or unstable nature of the hyporesponsiveness induced by the DC progenitors in nonimmunosuppressed recipients.