Danturti Sreedevi, Keslar Karen S, Steinhoff Leah R, Fan Ran, Dvorina Nina, Valujskikh Anna, Fairchild Robert L, Baldwin William M
Department of Immunology, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio, USA.
JCI Insight. 2017 Jun 15;2(12). doi: 10.1172/jci.insight.89641.
Adiponectin is a pleiotropic cytokine with diverse immunomodulatory effects on macrophages and lymphocytes. In the current paradigm, lymphocytes and macrophages respond to adiponectin that is produced by adipocytes and other parenchymal cells. Using a model of chronic arterial inflammation in cardiac transplants, we found that T cells derived from the recipient migrate to the heart and produce adiponectin locally. The evidence that T cells produce significant amounts of adiponectin is based on 3 experimental approaches. First, CD4+ T cells isolated from the blood and spleen after cardiac transplantation express mRNA for adiponectin. Second, reconstitution of T cell-deficient recipients with transgenic CD4+ T cells that express receptors for donor antigens results in arterial infiltrates containing T cells and increased mRNA expression for adiponectin in cardiac transplants. Third, CD4+ T cells isolated from the allograft secrete adiponectin in vitro. Taken together, these data indicate that adiponectin-competent cells originating in the recipient migrate into the transplant. Establishing T cells as a source of adiponectin provides a new dimension, to our knowledge, to the modulatory effects of adiponectin on immune responses.
脂联素是一种多效性细胞因子,对巨噬细胞和淋巴细胞具有多种免疫调节作用。在当前的模式中,淋巴细胞和巨噬细胞对脂肪细胞及其他实质细胞产生的脂联素作出反应。利用心脏移植慢性动脉炎症模型,我们发现受体来源的T细胞迁移至心脏并在局部产生脂联素。T细胞产生大量脂联素的证据基于三种实验方法。第一,心脏移植后从血液和脾脏分离出的CD4+ T细胞表达脂联素的mRNA。第二,用表达供体抗原受体的转基因CD4+ T细胞重建T细胞缺陷受体,会导致心脏移植中有含T细胞的动脉浸润以及脂联素的mRNA表达增加。第三,从同种异体移植物中分离出的CD4+ T细胞在体外分泌脂联素。综上所述,这些数据表明源自受体的有脂联素生成能力的细胞迁移至移植物中。据我们所知,确定T细胞为脂联素的来源为脂联素对免疫反应的调节作用提供了新的视角。