Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.
J Immunol. 2010 Nov 15;185(10):5907-14. doi: 10.4049/jimmunol.1000835. Epub 2010 Oct 13.
The costimulatory molecules in the B7-CD28 families are important in the regulation of T cell activation and tolerance. The butyrophilin family of proteins shares sequence and structure homology with B7 family molecules; however, the function of the butyrophilin family in the immune system has not been defined. In this study, we performed an analysis on multiple butyrophilin molecules and found that butyrophilin-like (BTNL)1 molecule functions to dampen T cell activation. BTNL1 mRNA was broadly expressed, but its protein was only found in APCs and not T cells. The putative receptor for BTNL1 was found on activated T cells and APCs. Also, recombinant BTNL1 molecule inhibited T cell proliferation by arresting cell cycle progression. The administration of neutralizing Abs against BTNL1 provoked enhanced T cell activation and exacerbated disease in autoimmune and asthma mouse models. Therefore, BTNL1 is a critical inhibitory molecule for T cell activation and immune diseases.
B7-CD28 家族中的共刺激分子在 T 细胞激活和耐受的调节中起着重要作用。 丁酰膦蛋白家族的蛋白与 B7 家族分子具有序列和结构同源性；然而，丁酰膦蛋白家族在免疫系统中的功能尚未确定。 在这项研究中，我们对多种丁酰膦蛋白分子进行了分析，发现丁酰膦蛋白样 1 分子（BTNL1）可抑制 T 细胞激活。 BTNL1 mRNA 广泛表达，但其蛋白仅在 APC 中而不在 T 细胞中发现。 BTNL1 的假定受体存在于活化的 T 细胞和 APC 上。 此外，重组 BTNL1 分子通过阻止细胞周期进程抑制 T 细胞增殖。 施用针对 BTNL1 的中和抗体可引发 T 细胞激活增强，并在自身免疫和哮喘小鼠模型中加重疾病。 因此，BTNL1 是 T 细胞激活和免疫疾病的关键抑制分子。
