Kosiewicz M M, Okamoto S, Miki S, Ksander B R, Shimizu T, Streilein J W
Department of Microbiology and Immunology, University of Miami School of Medicine, Fl.
J Immunol. 1994 Oct 1;153(7):2962-73.
Delayed hypersensitivity (DH) is an important immune effector modality that successfully wards off intracellular pathogens and many parasites, but also causes immunopathogenic injury to vital tissues. Particularly in the eye, DH has devastating effects that can lead to blindness. Ags injected into the anterior chamber of the eye of naive mice elicit a deviant form of systemic immunity in which DH is selectively down-regulated. Expression of DH in this model system is curtailed by regulatory CD8+ T cells. At present, we have determined whether injection of Ag into the anterior chamber of eyes of specifically sensitized mice also impairs DH expression. Our results indicate that DH is blunted or eliminated in previously primed mice when heterologous proteins, retinal autoantigens, or minor histocompatibility Ags are injected into the anterior chamber. Suppression is achieved in this system by Ag-specific CD8+ T cells, and failed DH can be imposed on immunized mice by i.v. injections of peritoneal exudate cells pulsed with Ag in vitro in the presence of TGF-beta. Thus, the immune regulatory mechanisms that operate to protect the eye from immunogenic inflammation can be invoked in previously sensitized mice. In addition, tolerance could not be generated in presensitized mice by either i.v. injection of soluble Ag or painting of hapten on UVB-exposed skin. It seems that the strategies used by the eye to create a deviant state of immunity in the face of pre-existing conventional immunity may be unique.
迟发型超敏反应（DH）是一种重要的免疫效应方式，它能成功抵御细胞内病原体和许多寄生虫，但也会对重要组织造成免疫致病损伤。特别是在眼睛中，DH具有毁灭性影响，可导致失明。将抗原注射到未致敏小鼠的眼前房会引发一种异常形式的全身免疫，其中DH会被选择性下调。在这个模型系统中，DH的表达受到调节性CD8⁺T细胞的抑制。目前，我们已确定将抗原注射到特异性致敏小鼠的眼前房是否也会损害DH的表达。我们的结果表明，当将异源蛋白、视网膜自身抗原或次要组织相容性抗原注射到眼前房时，先前致敏小鼠的DH会减弱或消除。在该系统中，抗原特异性CD8⁺T细胞实现了抑制作用，并且在存在转化生长因子-β的情况下，通过静脉注射体外经抗原脉冲处理的腹腔渗出细胞，可使免疫小鼠出现DH功能缺失。因此，在先前致敏的小鼠中，可以调用保护眼睛免受免疫原性炎症影响的免疫调节机制。此外，通过静脉注射可溶性抗原或在紫外线B照射的皮肤上涂抹半抗原，在预先致敏的小鼠中无法产生耐受性。看来，面对预先存在的传统免疫，眼睛用于创造异常免疫状态的策略可能是独特的。
