Sontheimer R D
J Invest Dermatol. 1985 Jul;85(1 Suppl):21s-26s. doi: 10.1111/1523-1747.ep12275423.
Earlier studies carried out in our laboratory which demonstrated that disaggregated human epidermal cells isolated from normal flexor forearm skin produced a greater degree of primary allogeneic lymphocyte blastogenic response than did autologous peripheral blood mononuclear cells have since been confirmed by others. We have now completed a series of additional studies designed to determine the basis for this difference. Blocking studies with anti-HLA-DR antibodies revealed that the allogeneic response triggered by epidermal cells was completely dependent on the presence of unbound HLA-DR molecules eliminating the possibility that nonspecific mitogenic effects produced by the epidermal cell suspension might be responsible for the difference. In addition we were unable to demonstrate that epidermal keratinocytes were supplying a nonspecific helper or growth-promoting effect to the interaction between stimulating HLA-DR bearing Langerhans cells and responding T lymphocytes. Since it has recently been suggested that the entire alloantigen-presenting capacity of unfractionated peripheral blood mononuclear cells can be attributed to a small population of HLA-DR antigen-bearing dendritic cells, we have considered the possibility that the greater degree of allogeneic lymphocyte response produced by epidermal cells could be due to the presence of a greater percentage of HLA-DR positive dendritic cells present in epidermal cell suspensions (i.e., Langerhans cells). Peripheral blood dendritic cell-enriched fractions and epidermal cell suspensions that contained similar percentages of dendritic cells produced equivalent amounts of allogeneic lymphocyte stimulation, whereas peripheral blood dendritic cell-enriched fractions that contained greater percentages of dendritic cells than were present in epidermal cell suspensions produced greater amounts of allogeneic stimulation. We therefore conclude that the enhanced mixed lymphocyte reaction stimulating capacity of human epidermal cell suspensions could be explained by the fact that epidermal cell suspensions contain a greater percentage of HLA-DR bearing alloantigen-presenting dendritic cells than do unfractionated peripheral blood mononuclear cell suspensions.
我们实验室早期开展的研究表明,从正常屈侧前臂皮肤分离出的分散人表皮细胞所产生的原发性同种异体淋巴细胞增殖反应程度,比自体外周血单个核细胞更高,这一结果后来得到了其他研究的证实。我们现在已经完成了一系列额外研究,旨在确定这种差异的基础。用抗HLA - DR抗体进行的阻断研究显示,表皮细胞引发的同种异体反应完全依赖于未结合的HLA - DR分子的存在,排除了表皮细胞悬液产生的非特异性促有丝分裂作用可能导致这种差异的可能性。此外,我们无法证明表皮角质形成细胞对刺激的携带HLA - DR的朗格汉斯细胞与反应性T淋巴细胞之间的相互作用提供非特异性辅助或促生长作用。由于最近有人提出,未分级的外周血单个核细胞的全部同种异体抗原呈递能力可归因于一小部分携带HLA - DR抗原的树突状细胞,我们考虑了表皮细胞产生更高程度同种异体淋巴细胞反应可能是由于表皮细胞悬液中存在更高百分比的HLA - DR阳性树突状细胞(即朗格汉斯细胞)的可能性。含有相似百分比树突状细胞的外周血富集树突状细胞组分和表皮细胞悬液产生等量的同种异体淋巴细胞刺激,而含有比表皮细胞悬液中更高百分比树突状细胞的外周血富集树突状细胞组分产生更大程度的同种异体刺激。因此,我们得出结论,人表皮细胞悬液增强的混合淋巴细胞反应刺激能力可以用以下事实来解释:与未分级的外周血单个核细胞悬液相比,表皮细胞悬液含有更高百分比的携带同种异体抗原呈递树突状细胞的HLA - DR。