Hara Y, Caspi R R, Wiggert B, Dorf M, Streilein J W
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
J Immunol. 1992 Sep 1;149(5):1531-8.
The selective deficit in delayed hypersensitivity that characterizes anterior chamber-associated immune deviation (ACAID) is the direct result of a blood borne, Ag-specific, cell-associated signal that is created after Ag is injected into the anterior chamber of the eye of normal mice. The cells that carry this signal via the blood to the spleen express the mature macrophage marker F4/80 and are similar to, or perhaps even arise from, F4/80+ dendritic cells found within the stroma of normal iris and ciliary body. We have recently reported that ACAID-inducing properties can be conferred upon conventional F4/80-bearing macrophages harvested from the normal peritoneal cavity by incubating these cells in vitro with the soluble protein Ag, BSA, in the presence of supernatants harvested from cultured iris and ciliary body cells. Using this in vitro induction system, we have examined the limiting conditions for conferring ACAID-inducing potential on peritoneal exudate cells. We have found that an ACAID-inducing signal can be created in vitro with several different soluble Ag, including the retinal autoantigen-interphotoreceptor retinol binding protein, and that active endocytosis and processing by peritoneal exudate cells is required because chloroquine prevents these cells from acquiring ACAID-inducing properties. In addition, we have determined that for supernatant-treated peritoneal macrophages to induce ACAID to soluble Ag the cells must be 1) alive, 2) injected i.v. or i.p. (but not s.c.), and 3) administered to recipients with an anatomically intact spleen. When these conditions are met, as few as 20 F4/80+ macrophages pulsed with Ag in the presence of iris and ciliary body supernatants are sufficient to induce ACAID. Macrophage hybridomas derived from "conventional" APC can acquire ACAID-inducing potential in vitro if exposed to iris and ciliary body supernatants, whereas macrophage hybridomas derived from "suppressor inducer" APC constitutively possess ACAID-induced potential. Peritoneal macrophages that were endowed with ACAID-inducing properties by in vitro exposure to supernatants were found to elicit splenic suppressor cells similar to those found in spleens of mice with ACAID. Moreover, the expression of experimental autoimmune uveitis in mice immunized with interphotoreceptor retinol binding protein was significantly suppressed if the animals were pretreated with peritoneal exudate cells pulsed with this Ag in the presence of iris and ciliary body supernatants.(ABSTRACT TRUNCATED AT 400 WORDS)
眼前房相关免疫偏离（ACAID）所特有的迟发型超敏反应中的选择性缺陷，是一种血源的、抗原特异性的、细胞相关信号的直接结果，该信号在抗原注入正常小鼠眼前房后产生。通过血液将这种信号携带至脾脏的细胞表达成熟巨噬细胞标志物F4/80，并且与正常虹膜和睫状体基质中发现的F4/80⁺树突状细胞相似，或者甚至可能起源于此。我们最近报道，通过在体外将从正常腹腔收获的携带常规F4/80的巨噬细胞与可溶性蛋白抗原牛血清白蛋白（BSA）一起在从培养的虹膜和睫状体细胞收获的上清液存在下孵育，可以赋予其ACAID诱导特性。使用这种体外诱导系统，我们研究了赋予腹腔渗出细胞ACAID诱导潜力的限制条件。我们发现，可以用几种不同的可溶性抗原在体外产生ACAID诱导信号，包括视网膜自身抗原——光感受器间维生素A结合蛋白，并且腹腔渗出细胞的活性内吞作用和加工是必需的，因为氯喹会阻止这些细胞获得ACAID诱导特性。此外，我们已经确定，对于经上清液处理的腹腔巨噬细胞诱导针对可溶性抗原的ACAID，细胞必须：1）存活，2）静脉内或腹腔内注射（但不是皮下注射），3）给予脾脏解剖结构完整的受体。当满足这些条件时，在虹膜和睫状体上清液存在下用抗原脉冲处理的低至20个F4/80⁺巨噬细胞就足以诱导ACAID。源自“常规”抗原呈递细胞（APC）的巨噬细胞杂交瘤如果暴露于虹膜和睫状体上清液，可以在体外获得ACAID诱导潜力，而源自“抑制诱导”APC的巨噬细胞杂交瘤则组成性地具有ACAID诱导潜力。通过体外暴露于上清液而具有ACAID诱导特性的腹腔巨噬细胞被发现可引发类似于ACAID小鼠脾脏中发现的脾抑制细胞。此外，如果在用该抗原在虹膜和睫状体上清液存在下脉冲处理的腹腔渗出细胞对动物进行预处理，则用视网膜间维生素A结合蛋白免疫的小鼠中实验性自身免疫性葡萄膜炎的表达会被显著抑制。（摘要截断于400字）
