Nguyen Loc T, Radhakrishnan Suresh, Ciric Bogoljub, Tamada Koji, Shin Tahiro, Pardoll Drew M, Chen Lieping, Rodriguez Moses, Pease Larry R
Department of Immunology, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester, MN 55905, USA.
J Exp Med. 2002 Nov 18;196(10):1393-8. doi: 10.1084/jem.20021466.
B7-DC molecules are known to function as ligands on antigen-presenting cells (APCs), enhancing T cell activation. In this study, cross-linking B7-DC with the monoclonal antibody sHIgM12 directly potentiates dendritic cell (DC) function by enhancing DC presentation of major histocompatibility complex-peptide complexes, promoting DC survival; and increasing secretion of interleukin (IL)-12p70, a key T helper cell type 1 promoting cytokine. Furthermore, ex vivo treatment of DCs or systemic treatment of mice with sHIgM12 increases the number of transplanted DCs that reach draining lymph nodes and increases the ability of lymph node APCs to activate naive T cells. Systemic administration of the antibody has an equivalent effect on DCs transferred at a distant site. These findings implicate B7-DC expressed on DCs in bidirectional communication. In addition to the established costimulatory and inhibitory functions associated with B7-DC, this molecule can also function as a conduit for extracellular signals to DCs modifying DC functions.
已知B7-DC分子作为抗原呈递细胞(APC)上的配体发挥作用,可增强T细胞活化。在本研究中,用单克隆抗体sHIgM12交联B7-DC可通过增强主要组织相容性复合体-肽复合物的树突状细胞(DC)呈递、促进DC存活以及增加白细胞介素(IL)-12p70(一种促进1型辅助性T细胞的关键细胞因子)的分泌,直接增强DC功能。此外,用sHIgM12对DC进行体外处理或对小鼠进行全身处理,可增加到达引流淋巴结的移植DC数量,并增强淋巴结APC激活初始T细胞的能力。抗体的全身给药对在远处部位转移的DC具有同等作用。这些发现表明DC上表达的B7-DC参与双向通讯。除了与B7-DC相关的既定共刺激和抑制功能外,该分子还可作为细胞外信号传导至DC的通道,从而改变DC功能。