Dermal injection of immunocytes induces psoriasis
Dermal injection of immunocytes induces psoriasis
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DOI：
10.1172/jci118989
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发表时间：
1996-10-15
影响因子：
15.9
通讯作者：
Nickoloff, BJ
中科院分区：
文献类型：
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作者：
WroneSmith, T;Nickoloff, BJ
由于缺乏动物模型，在银屑病中存在的活化细胞类型的联合体之间建立直接和因果关系受到阻碍。在银屑病斑块内，存在增生的角质形成细胞、浸润的免疫细胞和活化的内皮细胞。本研究的目的是确定银屑病是否主要是角质形成细胞或免疫系统的疾病，使用新开发的实验系统，其中全层人皮肤原位移植到严重联合免疫缺陷小鼠上，将自体免疫细胞注射到真皮中，并通过临床，组织学和免疫表型分析表征所得表型，植入的样品包括从别处患有银屑病的患者或从没有皮肤疾病的健康个体（NN皮肤）移除的未受累/无病变（PN）皮肤。在涉及6个不同银屑病患者的10个不同实验中，通过注射自体血液衍生的免疫细胞将每个PN皮肤转化为完全发育的银屑病斑块皮肤。在除了一个银屑病患者之外的所有患者中，免疫细胞需要用IL-2和超抗原预活化以将PN皮肤转化为银屑病斑块皮肤。在每种情况下，所得斑块的特征在于可见存在剥落和增厚的皮肤，颗粒细胞层的丧失、具有真皮血管生成组织反应的网钉显著伸长以及T细胞在表皮内的浸润。皮损皮肤显示银屑病表型的20种不同抗原决定簇。4例自体免疫细胞注射的NN皮肤样本均未转化为银屑病斑块。我们得出结论，银屑病主要是由致病性血液来源的免疫细胞诱导内源性皮肤细胞（包括角质形成细胞和血管内皮细胞）的二次活化和无序生长的能力引起的。
Establishing direct and causal relationships among the confederacy of activated cell types present in psoriasis has been hampered by lack of an animal model, Within psoriatic plaques there are hyperplastic keratinocytes, infiltrating immunocytes, and activated endothelial cells. The purpose of this study was to determine if psoriasis is primarily a disorder of keratinocytes or the immune system, Using a newly developed experimental system in which full-thickness human skin is orthotopically transferred onto severe combined immunodeficient mice, autologous immunocytes were injected into dermis, and the resultant phenotype characterized by clinical, histologic, and immunophenotypic analyses, Engraftment of samples included both uninvolved/ symptomless (PN) skin removed from patients with psoriasis elsewhere, or from healthy individuals with no skin disease (NN skin). In 10 different experiments involving 6 different psoriasis patients, every PN skin was converted to a full-fledged psoriatic plaque skin by injection of autologous blood-derived immunocytes, In all but one psoriatic patient, the immunocytes required preactivation with IL-2 and superantigens to convert PN skin into psoriatic plaque skin, In every case, resultant plaques were characterized by visible presence of flaking and thickened skin, loss of the granular cell layer, prominent elongation of rete pegs with a dermal angiogenic tissue reaction, and infiltration within the epidermis by T cells. Lesional skin displayed 20 different antigenic determinants of the psoriatic phenotype. None of the four NN skin samples injected with autologous immunocytes converted to psoriatic plaques, We conclude that psoriasis is caused primarily by the ability of pathogenetic blood-derived immunocytes to induce secondary activation and disordered growth of endogenous cutaneous cells including keratinocytes and vascular endothelium.