Study on the behavior and Immunophenotype of lymph nodal dendritic cells in normal and abnormal conditions

1998年，我们研究了人浅表淋巴结（LN）中的树突状细胞（DC）。我们发现淋巴结DC可分为三种类型。即，I-DC组为CD 1a +/CD 83-/CD 86-LC型未成熟DC，II-DC组为CD 1a-/CD 83 +/CD 86+成熟IDC，III-DC组为CD 1a +/CD 83-/CD 86-刺激的IDC。流式细胞术分析表明，绝大多数DC从浅表LN获得的II型DC。当组I-DC与自体淋巴结T细胞一起培养时，它们成熟为IDC。此外，当未成熟DC与自体LN T细胞在GM-CSF或IL-1的存在下培养时，它们成熟为类似于III组IDC的增生性IDC。这些研究结果表明，在浅表LN，LC型DC是连续提供的皮肤，他们大多经历细胞凋亡而不分化成IDC，这种抑制只发生在体内。1999年，我们进一步研究了DC在腹部LN中的表达，发现它们比正常人少得多。 关于我们 结论：在胃肠道粘膜-LN系统中，DC的迁移、成熟和凋亡等活性变化几乎不发生。我们还研究了利用单核细胞衍生的DC（MoDC）模型的DC的成熟过程。我们发现，用GM-CSF+IL-4+TGF-b1诱导的LC型未成熟MoDC在自体混合白细胞反应（MLR）中成熟为IDC，在同种异体MLR中它们大多发生凋亡，尽管它们强烈刺激同种异体T细胞的增殖。综上所述，我们假设如下：（1）在浅表LN中，相当数量的LC型未成熟DC从皮肤持续提供，而它们大多经历凋亡而不成熟为IDC。(2)T细胞非特异性地促进这些LC型未成熟DC成熟为IDC抗原。(3)用这些DC上表达的抗原刺激的抗原特异性T细胞抑制它们成熟为IDC，导致LC型未成熟DC的凋亡。(4)LN中的LC型未成熟DC有机会遇到许多对其所暴露的抗原具有特异性的T细胞，因为T细胞的连续循环，并且抗原活化的T细胞将其去除以避免过度免疫。我们认为DC在免疫监视中起主要作用，而不是加强和维持免疫应答。少

In 1998, we investigated dendritic cells (DC) in human superficial lymph nodes (LN). We found that lymph nodal DC can be classified into 3 groups. Namely, group I-DC is CD1a+/ CD83-/CD86- LC-type immature DC, group II-DC is CD1a-/CD83+/CD86+ mature IDC, and group III-DC is CD1a+/CD83-/CD86- stimulated IDC. Flow cytometric analysis indicated that the vast majority of DC obtained from the superficial LN were group-II DC. When group I-DC were cultured together with autologous lymph node T-cells, they matured into IDC. In addition, when immature DC were cultured with autologous LN T-cells in the presence of GM-CSF or IL-1, they matured into hyperplastic IDC resembling group-III IDC. These findings suggest that in superficial LN, LC-type DC are continuously provided from the skin, that they mostly undergo apoptosis without differentiating into IDC, and that this suppression takes place only in vivo. In 1999, we further investigated DC in the abdominal LN and found that they are much fewer t … More han those in the superficial LN, and that active changes of DC including migration, maturation and apoptosis may hardly take place in the gastrointestinal mucosa -LN system. We also investigated the maturation processes of DC taking advantage of the model of monocyte-derived DC (MoDC). We found that LC-type immature MoDC generated with GM-CSF+IL-4+TGF-b1 matured into IDC in autologous mixed leukocyte reaction (MLR), and that they mostly underwent apoptosis in allogenic MLR, although they strongly stimulated the proliferation of allogenic T-cells. Taken together, we hypothesize as follows ; (1) In superficial LN, a considerable number of LC-type immature DC are continuously provided from the skin, while they mostly undergo apoptosis without maturing into IDC. (2) T-cells promote these LC-type immature DC to mature into IDC antigen-nonspecifically. (3) Antigen-specific T-cells, which are stimulated with the antigens expressed on these DC, suppress their maturation into IDC, resulting in apoptosis of LC-type immature DC. (4) LC-type immature DC in LN have a opportunity to meet many T-cells specific for the antigens that they bare, because of the continuous circulation of T-cells, and antigen-activated T-cells remove them to avoid hyperimmunization. We consider that DC play a major role in immunological surveillance rather than strengthening and maintenance of immune responses. Less