de Kozak Y, Naud M C, Bellot J, Faure J P, Hicks D
Laboratoire d'Immunopathologie de l'Oeil, INSERM U 86, Université de Paris VI, France.
J Neuroimmunol. 1994 Nov;55(1):1-9. doi: 10.1016/0165-5728(94)90141-4.
Experimental autoimmune uveoretinitis (EAU) and endotoxin-induced uveitis (EIU), models for human ocular immunopathological syndromes, result in ocular inflammation in susceptible, but not in resistant rat strains. Moreover rapid photoreceptor degeneration occurs in susceptible rats developing EAU. In order to see whether differences in local ocular immune regulation may account for changes in resistance or susceptibility, we have examined the in vitro production of the cytotoxic cytokine tumor necrosis factor (TNF) by two resident ocular cell types, retinal Müller glia (RMG) and retinal pigmented epithelium (RPE). These cells were isolated and cultured in vitro from Lewis (Lew) (highly susceptible), Lew x Brown-Norway (BN) F1 hybrid (susceptible), BN and Long-Evans (LE) (resistant or poorly susceptible) rats. Constitutive production of the cytokine TNF, or its liberation in response to either interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS) alone, was very low in RMG and RPE cells, irrespective of the strain. It was strongly induced by combined treatment with IFN-gamma and LPS in Lew RMG and RPE cells (mean values of 140 and 150 pg/10(5) cells, respectively) and in Lew x BN F1 RMG and RPE cells (mean values of 125 and 190 pg/10(5) cells, respectively), much less so from BN RMG and RPE cells (30 and 20 pg/10(5) cells, respectively) and remained undetectable in LE RMG and RPE cells. Hence susceptibility to EAU and EIU in vivo is correlated with the extent of TNF production by these two cell types under in vitro conditions, which may play a key role in initiating or perpetuating local immune responses.
实验性自身免疫性葡萄膜视网膜炎（EAU）和内毒素诱导性葡萄膜炎（EIU）是人类眼部免疫病理综合征的模型，可在易感但非抗性大鼠品系中引发眼部炎症。此外，在发生EAU的易感大鼠中会出现快速的光感受器退化。为了探究局部眼部免疫调节的差异是否可解释抗性或易感性的变化，我们检测了两种眼部驻留细胞类型，即视网膜穆勒胶质细胞（RMG）和视网膜色素上皮细胞（RPE），在体外产生细胞毒性细胞因子肿瘤坏死因子（TNF）的情况。这些细胞是从Lewis（Lew）（高度易感）、Lew×Brown-Norway（BN）F1杂种（易感）、BN和Long-Evans（LE）（抗性或低易感性）大鼠中分离并在体外培养的。无论品系如何，RMG和RPE细胞中细胞因子TNF的组成性产生或其单独对干扰素-γ（IFN-γ）或脂多糖（LPS）的反应性释放都非常低。在Lew RMG和RPE细胞（分别为140和150 pg/10⁵细胞的平均值）以及Lew×BN F1 RMG和RPE细胞（分别为125和190 pg/10⁵细胞的平均值）中，IFN-γ和LPS联合处理强烈诱导了TNF的产生，而BN RMG和RPE细胞中诱导程度要低得多（分别为30和20 pg/10⁵细胞），在LE RMG和RPE细胞中仍未检测到。因此，体内对EAU和EIU的易感性与这两种细胞类型在体外条件下产生TNF的程度相关，这可能在启动或维持局部免疫反应中起关键作用。
