Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris
Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris
复制标题
DOI：
10.1073/pnas.0409569102
复制
发表时间：
2005-02-08
影响因子：
11.1
通讯作者：
Krueger, JG
中科院分区：
文献类型：
--
作者：
Chamian, F;Lowes, MA;Krueger, JG
寻常型银屑病是一种皮肤病，被认为是1型自身免疫反应的结果，它为研究创新免疫疗法期间靶病变组织中发生的变化提供了机会。为了获得对批准的生物疗法的反应的更全面的了解，我们研究了阿拉西普，这是一种CD 2结合融合蛋白。我们检测了T细胞、树突状细胞（DC）和一些炎症基因的表达。在22例患者中，55%的患者表现出明确的疾病组织学缓解，病变淋巴细胞减少73%，浸润性CD 8（+）细胞减少79%。只有组织学应答者显示炎性基因IFN-γ、信号转导子和转录激活子1、由IFN-γ诱导的单核因子、诱导型NO合酶、IL-8和IL-23亚基的组织表达显著降低。免疫组化检测CD 83（+）和CD 11 c（+）DCs的平行减少。因为我们观察到alefacept主要与T细胞而不是DC结合，所以我们认为T细胞是治疗的主要靶点，但DC和一系列1型炎性基因被协同抑制。
Psoriasis vulgaris, a skin disease that is considered to be the result of a type 1 autoimmune response, provides an opportunity for studying the changes that occur in a target-diseased tissue during innovative immunotherapies. To gain a more comprehensive picture of the response to an approved biological therapy, we studied allacept, which is a CD2 binding fusion protein. We examined T cells, dendritic cells (DCs), and expression of a number of inflammatory genes. In 22 patients, 55% demonstrated a clear histological remission of the disease, with a 73% reduction in lesional lymphocytes and a 79% decrease in infiltrating CD8(+) cells. Only histological responders showed marked reductions in the tissue expression of inflammatory genes IFN-gamma, signal transducer and activator of transcription 1, monokine induced by IFN-gamma, inducible NO synthase, IL-8, and IL-23 subunits. Parallel decreases in CD83(+) and CD11c(+) DCs also were measured by immunohistochemistry. Because we observed that alefacept binds primarily to T cells and not DCs, we suggest that T cells are the primary target for therapy, but that DCs and a spectrum of type 1 inflammatory genes are coordinately suppressed.