Department of Immunology, Peking University Health Science Center, Beijing, China.
Eur J Immunol. 2012 Sep;42(9):2419-30. doi: 10.1002/eji.201142320. Epub 2012 Jul 16.
Although caltreticulin (CRT) is mainly a residential ER protein, it is also expressed on the membrane surface of various types of cells exhibiting multiple functions. We report here that intraperitoneal administration of a soluble recombinant CRT fragment (rCRT/39-272) led to a substantial decrease in delayed type hypersensitivity (DTH) responses in BALB/c mice and EAE in C57BL/6 mice. In the recall response against keyhole limpet hemocyanin (KLH) in vitro, draining lymph node cells from the rCRT/39-272-treated mice produced less IFN-γ but more IL-4 as compared with the cells from the control group. The immunomodulating effect of intraperitoneally administered rCRT/39-272 was attributed to anti-CRT Abs thereby induced, because, in passive transfer experiments, the CRT-specific antiserum could suppress DTH in BALB/c mice. B-cell-deficient μMT mice were not susceptible to rCRT/39-272-mediated DTH suppression. Furthermore, CRT appears on the surface of murine T cells soon after activation and remains detectable (at relatively low level) by flow cytometry for approximately 5 days in vitro. Anti-CRT Abs were able to inhibit AKT phosphorylation, proliferation, and cytokine production by activated murine T cells. We propose that cell surface CRT could play a role in the function of effector T cells and may be considered a target for immunological manipulation.
虽然钙网织蛋白 (CRT) 主要是内质网驻留蛋白，但它也表达在具有多种功能的各种类型细胞的膜表面上。我们在这里报告，腹腔内给予可溶性重组 CRT 片段（rCRT/39-272）可导致 BALB/c 小鼠迟发型超敏反应（DTH）反应和 C57BL/6 小鼠 EAE 显著减少。在体外针对血蓝蛋白（KLH）的回忆反应中，与对照组相比，来自 rCRT/39-272 处理小鼠的引流淋巴结细胞产生的 IFN-γ 较少，但产生的 IL-4 较多。腹腔内给予 rCRT/39-272 的免疫调节作用归因于由此诱导的抗 CRT Abs，因为在被动转移实验中，CRT 特异性抗血清可抑制 BALB/c 小鼠的 DTH。B 细胞缺陷 μMT 小鼠不易受到 rCRT/39-272 介导的 DTH 抑制。此外，CRT 在外周血 T 细胞激活后很快出现在表面，并且在体外大约 5 天内通过流式细胞术可检测到（处于相对低水平）。抗 CRT Abs 能够抑制激活的小鼠 T 细胞的 AKT 磷酸化、增殖和细胞因子产生。我们提出，细胞表面 CRT 可能在效应 T 细胞的功能中起作用，并且可以被认为是免疫操作的靶标。
