Immunology Division, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
J Immunol. 2010 Apr 1;184(7):3514-25. doi: 10.4049/jimmunol.0900416. Epub 2010 Mar 5.
Butyrophilin (BTN) genes encode a set of related proteins. Studies in mice have shown that one of these, BTN1A1, is required for milk lipid secretion in lactation, whereas butyrophilin-like 2 is a coinhibitor of T cell activation. To understand these disparate roles of BTNs, we first compared the expression and functions of mouse Btn1a1 and Btn2a2. Btn1a1 transcripts were not restricted to lactating mammary tissue but were also found in virgin mammary tissue and, interestingly, spleen and thymus. In confirmation of this, BTN1A1 protein was detected in thymic epithelial cells. By contrast, Btn2a2 transcripts and protein were broadly expressed. Cell surface BTN2A2 protein, such as the B7 family molecule programmed death ligand 1, was upregulated upon activation of T cells. We next examined the potential of both BTN1A1 and BTN2A2 to interact with T cells. Recombinant Fc fusion proteins of murine BTN2A2 and, surprisingly BTN1A1, bound to activated T cells, suggesting the presence of one or more receptors on these cells. Immobilized BTN-Fc fusion proteins, but not MOG-Fc protein, inhibited the proliferation of CD4 and CD8 T cells activated by anti-CD3. BTN1A1 and BTN2A2 also inhibited T cell metabolism, IL-2, and IFN-gamma secretion. Inhibition of proliferation was not abrogated by exogenous IL-2 but could be overcome following costimulation with high levels of anti-CD28 Ab. These data are consistent with a coinhibitory role for mouse BTNs, including BTN1A1, the BTN expressed in the lactating mammary gland and on milk lipid droplets.
但是噬菌素（BTN）基因编码一组相关蛋白。小鼠研究表明，其中一种蛋白 BTN1A1 在泌乳期间对乳脂分泌是必需的，而 BTN 样蛋白 2 是 T 细胞激活的共抑制因子。为了了解 BTN 的这些不同作用，我们首先比较了小鼠 Btn1a1 和 Btn2a2 的表达和功能。Btn1a1 转录本不仅局限于泌乳期乳腺组织，也存在于处女期乳腺组织中，有趣的是，还存在于脾和胸腺中。这一点得到了 BTN1A1 蛋白在胸腺上皮细胞中检测到的证实。相比之下，Btn2a2 转录本和蛋白广泛表达。细胞表面 BTN2A2 蛋白，如程序性死亡配体 1 等 B7 家族分子，在 T 细胞激活时上调。接下来，我们研究了 BTN1A1 和 BTN2A2 与 T 细胞相互作用的潜力。重组的鼠 BTN2A2 和令人惊讶的 BTN1A1 的 Fc 融合蛋白与激活的 T 细胞结合，这表明这些细胞上存在一个或多个受体。固定化的 BTN-Fc 融合蛋白，但不是 MOG-Fc 蛋白，可抑制由抗 CD3 激活的 CD4 和 CD8 T 细胞的增殖。BTN1A1 和 BTN2A2 还抑制 T 细胞代谢、IL-2 和 IFN-γ的分泌。增殖抑制不能被外源性 IL-2 消除，但可通过高浓度抗 CD28 Ab 共刺激来克服。这些数据与鼠 BTN 的共抑制作用一致，包括 BTN1A1，它在泌乳期乳腺和乳脂滴中表达。
