Christofidou-Solomidou M, Albelda S M, Bennett F C, Murphy G F
Department of Dermatology, University of Pennsylvania Medical Center, Philadelphia, USA.
Am J Pathol. 1997 Feb;150(2):631-9.
Human dermatitis-involving cytotoxic interaction between effector lymphocytes and epithelial target cells has thus far been documented in vivo only as naturally occurring disease or as an iatrogenic complication of organ engraftment. In this report, we reproduce human cytotoxic dermatitis via local microinjection of heterologous human lymphocytes into human skin xenografted to mice with severe combined immune deficiency syndrome. Injection sites develop progressive T cell epidermotropism culminating in cytotoxic dermatitis resembling human lichen planus within 4 weeks. Effector T cells express a CD8+, TIA-1+ phenotype, proliferate locally, express interleukin-2 surface receptors, and demonstrate interferon-gamma mRNA induction after microinjection. Migration of these T cells into the epidermis is closely linked to experimental induction and coincident expression of intercellular adhesion molecule by keratinocytes. T cell apposition to keratinocytes is associated with endonuclease-mediated DNA fragmentation (apoptosis) in the latter cell type. Intraepidermal T cell migration and related lesion formation is partially abrogated by systemic administration of antisense oligonucleotide to ICAM-1 mRNA. These findings demonstrate that human cytotoxic tissue injury directed against epithelial targets can be produced and modulated in chimeric mice.
迄今为止，涉及效应淋巴细胞与上皮靶细胞之间细胞毒性相互作用的人类皮炎，仅在体内作为自然发生的疾病或作为器官移植的医源性并发症被记录下来。在本报告中，我们通过将异种人类淋巴细胞局部显微注射到移植到重症联合免疫缺陷综合征小鼠体内的人类皮肤异种移植物中，再现了人类细胞毒性皮炎。注射部位出现渐进性T细胞向表皮趋化，最终在4周内发展为类似人类扁平苔藓的细胞毒性皮炎。效应T细胞表达CD8 +、TIA - 1 +表型，在局部增殖，表达白细胞介素 - 2表面受体，并在显微注射后显示γ干扰素mRNA诱导。这些T细胞向表皮的迁移与角质形成细胞对细胞间粘附分子的实验性诱导和同时表达密切相关。T细胞与角质形成细胞的并置与后者细胞类型中核酸内切酶介导的DNA片段化（凋亡）有关。全身给予ICAM - 1 mRNA的反义寡核苷酸可部分消除表皮内T细胞迁移和相关病变形成。这些发现表明，针对上皮靶标的人类细胞毒性组织损伤可以在嵌合小鼠中产生并受到调节。
