A small number of anti-CD3 molecules on dendritic cells stimulate DNA synthesis in mouse T lymphocytes.
A small number of anti-CD3 molecules on dendritic cells stimulate DNA synthesis in mouse T lymphocytes.
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DOI：
10.1084/jem.169.3.1153
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发表时间：
1989-03-01
期刊：
影响因子：
--
通讯作者：
Steinman RM
中科院分区：
文献类型：
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作者：
Romani N;Inaba K;Puré E;Crowley M;Witmer-Pack M;Steinman RM
当用抗CD3 mAb和带有FC受体（FCR）的抗CD3 MAB和辅助细胞挑战时，静止的T细胞进入细胞周期。抗CD3的表现被认为是辅助细胞向TCR复合物提出的抗原的模型。我们获得了证据，表明与辅助细胞相关的抗CD3分子的数量可能很小。我们首先注意到胸腺树突状细胞和培养，但没有新鲜分离的表皮兰格汉细胞（LC）是活性辅助细胞，以反应抗CD3 mAb。 DNA合成被mAb与FCR废除，而不是通过mAb与克隆特异性抗原识别的其他分子，即I类和II类MHC产物或CD4和CD8。必要的FCR可以在LC上识别，但数量很少。新鲜分离的LC每个细胞具有20,000 FCR，而更活跃的LC只有2,000个位点，在定量结合研究中使用125i-Anti-fcr mAb。单个LC具有相似的FCR水平，敏感的FACS证明。在有丝分裂作用反应开始或期间，在T细胞或树突细胞细胞质内无法检测到FCR。当通过单细胞测定时评估30小时的响应时，每个添加的LC至少20个T细胞变成淋巴细胞，至少8个T细胞在与离散细胞簇中接触时合成DNA。在某种程度上，抗CD3代表了针对特定T细胞克隆的抗原呈递的多克隆模型，这些结果表明了两个结论。首先，可能需要树突状细胞上的配体分子200-300个分子来触发T细胞。其次，培养物中LC的成熟需要“敏化”功能（FCR上的抗CD3）对clonotypic T细胞受体。
Resting T cells enter cell cycle when challenged with anti-CD3 mAb and accessory cells that bear required Fc receptors (FcR). Presentation of anti-CD3 is thought to be a model for antigens presented by accessory cells to the TCR complex. We have obtained evidence that the number of anti-CD3 molecules that are associated with the accessory cell can be very small. We first noticed that thymic dendritic cells and cultured, but not freshly isolated, epidermal Langerhans cells (LC) were active accessory cells for responses to anti-CD3 mAb. DNA synthesis was abrogated by a mAb to the FcR but not by mAb to other molecules used in clonally specific antigen recognition, i.e., class I and II MHC products or CD4 and CD8. The requisite FcR could be identified on the LC but in small numbers. Freshly isolated LC had 20,000 FcR per cell, while the more active cultured LC had only 2,000 sites, using 125I-anti- FcR mAb in quantitative binding studies. Individual LC had similar levels of FcR, as evidenced with a sensitive FACS. FcR could not be detected on T cells or within the dendritic cell cytoplasm, at the start of or during the mitogenesis response. When the response was assessed at 30 h with single cell assays, at least 20 T cells became lymphoblasts per added LC, and at least 8 T cells were synthesizing DNA while in contact with the LC in discrete cell clusters. To the extent that anti-CD3 represents a polyclonal model for antigen presentation to specific T cell clones, these results suggest two conclusions. First, only 200-300 molecules of ligand on dendritic cells may be required to trigger a T cell. Second, the maturation of LC in culture entails "sensitizing" functions other than ligand presentation (anti-CD3 on FcR) to clonotypic T cell receptors.