Roberge F G, Caspi R R, Nussenblatt R B
Laboratory of Immunology, National Eye Institute, Bethesda, MD 20892.
J Immunol. 1988 Apr 1;140(7):2193-6.
The Müller cell is the major glial element of the mammalian retina. It can be induced to express MHC class II determinants in culture, when exposed to supernatant from activated lymphocytes. In an in vitro co-culture system, Müller cells had been shown to exert a profound inhibitory influence on Ag- and IL-2-driven proliferation of Th cell lines. In the present report we demonstrate that Müller cells can produce IL-1 activity, and that in conditions where their inhibitory action is suppressed, they display the capacity to efficiently function as APC. Mildly trypsinized and glutaraldehyde-fixed Müller cells that had been preincubated with Ag and IFN-gamma-containing rat spleen conditioned medium were able to present Ag to an S-Ag specific Th lymphocyte line, which has the capacity to induce a severe uveoretinitis in rats. Addition of the Ag after fixation did not result in presentation, showing that Müller cells had to process the nominal Ag into an immunogenic form. It was also found that the efficiency of presentation was greatly increased in the presence of naive syngeneic or allogeneic accessory cells. This enhancing effect could not be reproduced with rIL-1. This report extends our ongoing study of interactions between the retinal glial Müller cell and T lymphocytes. The results show that these interactions can be diverse, even opposite in different conditions, and suggest the possibility that Müller cells could play a determining role in the course of immune reactions at the level of the neuro-retina.
米勒细胞是哺乳动物视网膜中的主要神经胶质成分。在培养过程中,当暴露于活化淋巴细胞的上清液时,它可被诱导表达II类主要组织相容性复合体(MHC)决定簇。在体外共培养系统中,已表明米勒细胞对Th细胞系的抗原和白细胞介素-2驱动的增殖具有深远的抑制作用。在本报告中,我们证明米勒细胞可产生白细胞介素-1活性,并且在其抑制作用被抑制的条件下,它们表现出有效作为抗原呈递细胞(APC)发挥作用的能力。预先用抗原和含γ干扰素的大鼠脾脏条件培养基孵育的轻度胰蛋白酶处理和戊二醛固定的米勒细胞,能够将抗原呈递给一种对S抗原特异的Th淋巴细胞系,该细胞系有能力在大鼠中诱导严重的葡萄膜视网膜炎。固定后添加抗原不会导致呈递,这表明米勒细胞必须将名义上的抗原加工成免疫原性形式。还发现,在存在同基因或异基因幼稚辅助细胞的情况下,呈递效率大大提高。用重组白细胞介素-1无法重现这种增强作用。本报告扩展了我们正在进行的关于视网膜神经胶质米勒细胞与T淋巴细胞之间相互作用的研究。结果表明,这些相互作用可能多种多样,甚至在不同条件下相反,并提示米勒细胞可能在神经视网膜水平的免疫反应过程中起决定性作用。