Bone marrow-derived dendritic cell progenitors (NLDC 145(+), MHC class II+, B7-1(dim), B7-2(-)) induce alloantigen-specific hyporesponsiveness in murine T lymphocytes
Bone marrow-derived dendritic cell progenitors (NLDC 145(+), MHC class II+, B7-1(dim), B7-2(-)) induce alloantigen-specific hyporesponsiveness in murine T lymphocytes
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DOI：
10.1097/00007890-199560120-00028
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发表时间：
1995-12-27
期刊：
影响因子：
6.2
通讯作者：
Thomson, AW
中科院分区：
文献类型：
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作者：
Lu, L;McCaslin, D;Thomson, AW
树突状细胞（DC）和其他抗原呈递细胞的功能成熟被认为反映了细胞表面主要组织相容性复合物（MHC）II类和其他T细胞共刺激分子，特别是CD 28配体B7-1（CD 80）和B7-2（CD 86）的上调。我们从B10小鼠（H-2（B）; I-A（+））的骨髓（BM）中增殖了响应粒细胞-巨噬细胞集落刺激因子（GM-CSF）的表现出DC前体特征的细胞。所使用的方法类似于先前用于从正常小鼠肝脏增殖DC祖细胞的那些方法。从8-10天GM-CSF刺激的BM细胞培养物收获的（NLDC 145（+），33 D1（+），N418（+））是CD 45（+）热稳定抗原（+），CD 54（+），CD 44（+），MHC II类+，B7-1（暗淡），但B7-2（-）（共刺激分子缺陷）。然而，除了GM-CSF之外，补充白细胞介素-4（IL-4）的培养物导致MHC II类和B7-2表达的显著上调。后者细胞在原代混合白细胞培养中表现出强的同种刺激活性。相反，单独用GM-CSF刺激的细胞是相对弱的刺激物，并且在二次MLR中检测到在再刺激时在同种异体T细胞中诱导同种抗原特异性低反应性（C3 H; H-2（k）; I-E（+））。对第三方刺激物的反应性是完整的，由GM-CSF刺激的共刺激分子缺陷的细胞诱导的低反应性通过在原代MLR中掺入抗CD 28单克隆抗体来防止，并且通过向再刺激的T细胞添加IL-2来逆转。结果表明，具有DC前体表型的MHC II类+ B7-2-细胞可以在体外诱导同种抗原特异性低反应性。在适当的条件下，这种共刺激分子缺陷的细胞可能有助于诱导体内供体特异性无反应性。
The functional maturation of dendritic cells (DC) and other antigen-presenting cells is believed to reflect the upregulation of cell surface major histocompatibility complex (MHC) class II and other T cell costimulatory molecules, especially the CD28 ligands B7-1 (CD80) and B7-2 (CD86), In this study, we propagated cells exhibiting characteristics of DC precursors from the bone marrow (BM) of B10 mice (H-2(b); I-A(+)) in response to granulocyte-macrophage colony stimulating factor (GM-CSF). The methods used were similar to those employed previously to propagate DC progenitors from normal mouse liver, Cells expressing DC lineage markers (NLDC 145(+), 33D1(+), N418(+)) harvested from 8-10-day GM-CSF stimulated BM cell cultures were CD45(+) heat-stable antigen(+), CD54(+), CD44(+), MHC class II+, B7-1(dim) but B7-2(-) (costimulatory molecule-deficient). Supplementation of cultures with interleukin-4 (IL-4) in addition to GM-CSF however, resulted in marked upregulation of MHC class II and B7-2 expression. These latter cells exhibited potent allostimulatory activity in primary mixed leukocyte cultures, In contrast, the cells stimulated with GM-CSF alone were relatively weak stimulators and induced alloantigen-specific hyporesponsiveness in allogeneic T cells (C3H; H-2(k); I-E(+)) detected upon restimulation in secondary MLR, This was associated with blockade of IL-2 production. Reactivity to third-party stimulators was intact, The hyporesponsiveness induced by the GM-CSF stimulated, costimulatory molecule-deficient cells was prevented by incorporation of anti-CD28 monoclonal antibody in the primary MLR and was reversed by addition of IL-2 to restimulated T cells, The findings show that MHC class II+ B7-2- cells with a DC precursor phenotype can induce alloantigen-specific hyporesponsiveness in vitro. Under the appropriate conditions, such costimulatory molecule-deficient cells could contribute to the induction of donor-specific unresponsiveness in vivo.