Swanson Kena A, Zheng Yan, Heidler Kathleen M, Mizobuchi Teruaki, Wilkes David S
Department of Microbiology and Immunology, Indiana University School of Medicine, 1001 West Tenth Street, OPW 425, Indianapolis, IN 46202, USA.
Am J Respir Cell Mol Biol. 2004 Mar;30(3):311-8. doi: 10.1165/rcmb.2003-0268OC. Epub 2003 Sep 4.
Interactions between antigen-presenting cells and T cells can result in T cell activation or suppression. With the use of RNA analysis, high-performance liquid chromatography, mixed leukocyte reactions (MLRs), and animal models, the current study reports that lung interstitial antigen-presenting cells (iAPCs, CDllc+) suppress T cell responses in vitro and in vivo by production of indoleamine 2,3-dioxygenase (IDO), an enzyme that catabolizes tryptophan to its byproduct, kynurenine. IDO mRNA expression was unique to lung iAPCs, as cells similarly isolated from the liver and spleen did not express IDO constitutively, or in response to interferon-gamma. Lung iAPCs suppressed proliferation of allogeneic T cells, correlating with increased kynurenine levels; and blockade of IDO activity with 1-methyl-DL-tryptohan (1-MT) or addition of exogenous tryptophan recovered T cell proliferation in MLRs. In contrast, liver and splenic iAPCs were potent stimulators of T cells in MLRs, and IDO inhibition had no effect on T cell responses. In vivo studies showed that systemic blockade of IDO resulted in spontaneous proliferation in lung T cells and pulmonary inflammation. Finally, overexpressing IDO in lung transplants abrogated acute allograft rejection, a T cell-mediated disease. Collectively these data show that lung iAPCs contribute to local regulation of cellular immune responses by production of IDO.
抗原呈递细胞与T细胞之间的相互作用可导致T细胞激活或抑制。通过RNA分析、高效液相色谱、混合淋巴细胞反应（MLR）及动物模型，本研究报告称，肺间质抗原呈递细胞（iAPC，CD11c+）通过产生吲哚胺2,3-双加氧酶（IDO）在体外和体内抑制T细胞反应，IDO是一种将色氨酸分解为其副产品犬尿氨酸的酶。IDO mRNA表达是肺iAPC所特有的，因为从肝脏和脾脏中类似分离出的细胞不组成性表达IDO，也不响应干扰素-γ表达IDO。肺iAPC抑制同种异体T细胞的增殖，这与犬尿氨酸水平升高相关；用1-甲基-DL-色氨酸（1-MT）阻断IDO活性或添加外源性色氨酸可恢复MLR中T细胞的增殖。相比之下，肝脏和脾脏的iAPC在MLR中是T细胞的有效刺激物，IDO抑制对T细胞反应没有影响。体内研究表明，全身阻断IDO会导致肺T细胞自发增殖和肺部炎症。最后，在肺移植中过表达IDO可消除急性同种异体移植排斥反应，这是一种T细胞介导的疾病。这些数据共同表明，肺iAPC通过产生IDO参与细胞免疫反应的局部调节。
