Griffiths C E, Voorhees J J, Nickoloff B J
Department of Dermatology, University of Michigan Medical Center, Ann Arbor.
J Am Acad Dermatol. 1989 Apr;20(4):617-29. doi: 10.1016/s0190-9622(89)70073-6.
Lymphocytes bind to cultured keratinocytes that are treated with interferon gamma (IFN-gamma) and tumor necrosis factor (TNF). When the lymphocytes are preincubated with antibody to lymphocyte function associated antigen-1 (LFA-1), this adherence is inhibited. Because intercellular adhesion molecule-1 (ICAM-1) is a ligand for LFA-1, we studied the cellular expression of ICAM-1, as well as two other IFN-gamma-inducible antigens, (HLA) human lymphocyte antigens DR and DQ, in both normal and diseased skin. The modulation of these cell surface antigens by IFN-gamma and TNF with the use of short-term organ cultures of skin was compared with isolated keratinocytes grown in a conventional tissue culture system. While in normal skin, keratinocytes did not express HLA-DR, DQ, or ICAM-1, when organ cultures were supplemented with IFN-gamma, rapid induction of keratinocyte ICAM-1 expression occurred after 24 hours; HLA-DR but not DQ expression occurred after 48 hours. TNF also induced keratinocyte ICAM-1 expression (although to a lesser degree than IFN-gamma) but did not induce either keratinocyte HLA-DR or DQ expression. There was good correlation of keratinocyte expression of ICAM-1 and HLA-DR by IFN-gamma and TNF when the epidermis of the organ culture system was compared with the isolated keratinocytes grown in tissue culture. The presence of intraepidermal lymphocytes correlated extremely well with keratinocyte ICAM-1 expression but not with keratinocyte HLA-DR expression in psoriasis, atopic dermatitis, lichen planus, and mycosis fungoides. The intensity of endothelial cell expression of ICAM-1 correlated with the degree of dermal inflammation. We conclude that IFN-gamma, once produced by activated T lymphocytes in the dermis, may be of importance in lymphocyte trafficking in the epidermis by the induction of keratinocyte ICAM-1 expression. The use of the short-term organ culture system, in which there is inducible ICAM-1 expression, provides an experimental bridge between purely in vitro and in vivo investigations to further our understanding of the molecular basis for lymphocyte apposition to keratinocytes in the skin.
淋巴细胞可与经γ干扰素（IFN-γ）和肿瘤坏死因子（TNF）处理的培养角质形成细胞结合。当淋巴细胞预先与抗淋巴细胞功能相关抗原-1（LFA-1）的抗体一起孵育时，这种黏附作用会受到抑制。由于细胞间黏附分子-1（ICAM-1）是LFA-1的配体，我们研究了正常皮肤和病变皮肤中ICAM-1以及另外两种IFN-γ诱导抗原，即（HLA）人类淋巴细胞抗原DR和DQ的细胞表达情况。通过皮肤短期器官培养，比较了IFN-γ和TNF对这些细胞表面抗原的调节作用，并与在传统组织培养系统中生长的分离角质形成细胞进行了对比。在正常皮肤中，角质形成细胞不表达HLA-DR、DQ或ICAM-1，但在器官培养物中添加IFN-γ后，24小时后角质形成细胞ICAM-1表达迅速诱导产生；48小时后出现HLA-DR表达，但未出现DQ表达。TNF也可诱导角质形成细胞ICAM-1表达（尽管程度低于IFN-γ），但既不诱导角质形成细胞HLA-DR表达，也不诱导DQ表达。当将器官培养系统的表皮与在组织培养中生长的分离角质形成细胞进行比较时，IFN-γ和TNF诱导的角质形成细胞ICAM-1和HLA-DR表达具有良好的相关性。在银屑病、特应性皮炎、扁平苔藓和蕈样肉芽肿中，表皮内淋巴细胞的存在与角质形成细胞ICAM-1表达密切相关，但与角质形成细胞HLA-DR表达无关。内皮细胞ICAM-1表达的强度与真皮炎症程度相关。我们得出结论，一旦真皮中活化的T淋巴细胞产生IFN-γ，可能通过诱导角质形成细胞ICAM-1表达在表皮淋巴细胞迁移中发挥重要作用。短期器官培养系统中存在可诱导的ICAM-1表达，为进一步理解皮肤中淋巴细胞与角质形成细胞附着的分子基础，在纯粹的体外研究和体内研究之间提供了一个实验桥梁。
