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活化淋巴细胞上皮肤淋巴细胞抗原的表达及其与IL-12R(β1和β2)、IL-2Rα和CXCR3的关联。

Cutaneous lymphocyte antigen expression on activated lymphocytes and its association with IL-12R (beta1 and beta2), IL-2Ralpha, and CXCR3.

作者信息

Reddy Manjula, Davis Cuc, Wong Jackson, Prabhakar Uma

机构信息

Department of Clinical Pharmacology and Experimental Medicine, Centocor Inc., 145 King of Prussia Road, Radnor, PA 19087-4517, USA.

出版信息

Cell Immunol. 2005 Jul-Aug;236(1-2):131-9. doi: 10.1016/j.cellimm.2005.08.019. Epub 2005 Sep 12.

Abstract

The majority of T lymphocytes that infiltrate psoriatic lesions express cutaneous lymphocyte antigen (CLA), a skin homing receptor involved in the influx of memory T cells to cutaneous sites. We investigated CLA expression on normal human peripheral blood mononuclear cells (PBMCs) and evaluated its association with IL-12 receptors, chemokine receptor, CXCR3, and IL-2Ralpha. PBMCs were stimulated in vitro with or without polyclonal activators (mitogen, or superantigens, or anti-CD3+anti-CD28) in the presence or absence of exogenous rhIL-12. The percentage of CLA+ T lymphocytes increased significantly after superantigen stimulation compared to anti-CD3+anti-CD28 or mitogen activation. The majority of activation induced CLA+ T lymphocytes co-expressed IL-12Rbeta1, IL-12Rbeta2, CXCR3, and CD25 in the presence of rhIL-12. Our results indicate that CLA expression on activated T lymphocytes is IL-12 and activation dependent and correlates with the expression of IL-12 receptors, IL-2Ralpha, and CXCR3. Monitoring the levels of Th1 differentiation markers such as CXCR3 and IL-12Rbeta2 along with activation marker, CD25 on skin homing CLA+ T lymphocytes may provide insight into the mechanism of action of immunotherapies directed against Th1 type skin inflammatory diseases.

摘要

浸润银屑病皮损的大多数T淋巴细胞表达皮肤淋巴细胞抗原(CLA),这是一种参与记忆T细胞流入皮肤部位的皮肤归巢受体。我们研究了CLA在正常人外周血单个核细胞(PBMC)上的表达,并评估了其与IL-12受体、趋化因子受体CXCR3和IL-2Rα的关联。在有或无外源性重组人IL-12的情况下,用或不用多克隆激活剂(丝裂原、超抗原或抗CD3 +抗CD28)体外刺激PBMC。与抗CD3 +抗CD28或丝裂原激活相比,超抗原刺激后CLA + T淋巴细胞的百分比显著增加。在重组人IL-12存在的情况下,大多数激活诱导的CLA + T淋巴细胞共表达IL-12Rβ1、IL-12Rβ2、CXCR3和CD25。我们的结果表明,活化T淋巴细胞上的CLA表达依赖于IL-12和激活,并与IL-12受体、IL-2Rα和CXCR3的表达相关。监测皮肤归巢CLA + T淋巴细胞上Th1分化标志物如CXCR3和IL-12Rβ2的水平以及激活标志物CD25,可能有助于深入了解针对Th1型皮肤炎症性疾病的免疫治疗作用机制。

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