Dix Richard D, Podack Eckhard R, Cousins Scott W
Harvery and Bernice Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Antiviral Res. 2003 Jul;59(2):111-9. doi: 10.1016/s0166-3542(03)00066-4.
Mice with a retrovirus-induced immunosuppression (MAIDS) are susceptible to experimental murine cytomegalovirus (MCMV) retinitis, but can be rendered resistant to retinitis by systemic interleukin-2 (IL-2) immunotherapy. Experiments were performed to explore the mechanism by which IL-2 treatment during MAIDS might restore resistance to MCMV retinitis. Whereas 80% of untreated MAIDS mice were susceptible to MCMV retinitis, none (0%) of IL-2-treated MAIDS mice developed necrotizing retinitis. In comparison, 100% of both untreated and IL-2-treated perforin knockout mice (PKO mice) were susceptible to MCMV retinitis, and severity of retinitis and amounts of infectious intraocular MCMV in IL-2-treated PKO mice were equivalent to that in untreated PKO mice. A competitive quantitative RT-PCR assay was used to measure the levels of perforin mRNA within MCMV-infected eyes of immunologically normal mice, untreated MAIDS mice, and IL-2-treated MAIDS mice. Although the level of perforin mRNA within MCMV-infected eyes of untreated MAIDS mice susceptible to retinitis was significantly reduced when compared to the high level found within MCMV-infected eyes of normal mice resistant to retinitis, systemic treatment of MAIDS mice with IL-2 increased perforin mRNA within MCMV-infected eyes to levels found in normal mice. The ability of IL-2 treatment to increase intraocular levels of perforin mRNA diminished with the progression of MAIDS. Our findings support the hypothesis that systemic IL-2 immunotherapy during MAIDS provides protection against MCMV retinitis by upregulation of perforin-mediated cytotoxicity used by cytotoxic lymphocytes to kill virus-infected cells.
患有逆转录病毒诱导免疫抑制（MAIDS）的小鼠易患实验性鼠巨细胞病毒（MCMV）视网膜炎，但通过全身性白细胞介素-2（IL-2）免疫疗法可使其对视网膜炎产生抗性。进行实验以探究在MAIDS期间进行IL-2治疗可能恢复对MCMV视网膜炎抗性的机制。未经治疗的MAIDS小鼠中有80%易患MCMV视网膜炎，而接受IL-2治疗的MAIDS小鼠无一（0%）发生坏死性视网膜炎。相比之下，未经治疗和接受IL-2治疗的穿孔素基因敲除小鼠（PKO小鼠）中有100%易患MCMV视网膜炎，且接受IL-2治疗的PKO小鼠的视网膜炎严重程度和眼内感染性MCMV数量与未经治疗的PKO小鼠相当。采用竞争性定量RT-PCR测定法来测量免疫正常小鼠、未经治疗的MAIDS小鼠以及接受IL-2治疗的MAIDS小鼠的MCMV感染眼中穿孔素mRNA的水平。尽管与对视网膜炎有抗性的正常小鼠的MCMV感染眼中发现的高水平相比，易患视网膜炎的未经治疗的MAIDS小鼠的MCMV感染眼中穿孔素mRNA的水平显著降低，但用IL-2对MAIDS小鼠进行全身治疗可使MCMV感染眼中的穿孔素mRNA增加至正常小鼠中的水平。随着MAIDS的进展，IL-2治疗增加眼内穿孔素mRNA水平的能力减弱。我们的研究结果支持以下假设：MAIDS期间的全身性IL-2免疫疗法通过上调细胞毒性淋巴细胞用于杀死病毒感染细胞的穿孔素介导的细胞毒性来提供针对MCMV视网膜炎的保护。
