Dix R D, Cray C, Cousins S W
Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Fla., USA.
Ophthalmic Res. 1997;29(6):381-92. doi: 10.1159/000268039.
Passive-transfer studies were performed to assess the ability of antibody alone to reduce the frequency and/or severity of necrotizing retinitis caused by murine cytomegalovirus (MCMV) in C57BL/6 mice with retrovirus-induced immunodeficiency syndrome (MAIDS). Initial experiments showed a gradual decline in the ability of mice to initiate humoral immunity during the evolution of MAIDS so that neither MCMV-specific IgM nor IgG could be detected during late-stage MAIDS. Passively administered hyperimmune MCMV immunoglobulin, however, could be detected within the serum of mice with MAIDS for at least 9 days after intraperitoneal injection and protected these animals in preliminary experiments from systemic MCMV disease and death when administered 24 h prior to intraperitoneal challenge with a lethal dose of virus. Nonetheless, passive transfer of hyperimmune MCMV serum to mice with MAIDS failed to reduce intraocular MCMV titers, frequency of retinitis, or severity of retinitis when administered 24 h prior to subretinal MCMV inoculation. Whereas whole eyes of MAIDS animals that received normal mouse serum and were injected subretinally with MCMV had an ocular MCMV titer of 4.3 log10 and a frequency of retinitis of 89% (severity score = 55%), whole eyes of antibody-treated mice with MAIDS had an ocular MCMV titer of 4.3 log10 and a frequency of retinitis of 87% (severity score = 57 %). Passive transfer of a neutralizing MCMV-specific monoclonal antibody also failed to reduce the frequency or severity of MCMV retinitis when administered to mice with MAIDS prior to subretinal MCMV inoculation. Our findings suggest that antibody immunotherapy alone will not be effective therapeutically for cytomegalovirus retinitis in patients with AIDS.
进行了被动转移研究,以评估单独抗体在患有逆转录病毒诱导免疫缺陷综合征(MAIDS)的C57BL/6小鼠中降低由鼠巨细胞病毒(MCMV)引起的坏死性视网膜炎频率和/或严重程度的能力。初步实验表明,在MAIDS演变过程中,小鼠启动体液免疫的能力逐渐下降,因此在晚期MAIDS期间无法检测到MCMV特异性IgM或IgG。然而,被动给予的超免疫MCMV免疫球蛋白,在腹腔注射后至少9天可在患有MAIDS的小鼠血清中检测到,并且在初步实验中,当在腹腔注射致死剂量病毒前24小时给予时,可保护这些动物免受全身性MCMV疾病和死亡。尽管如此,当在视网膜下接种MCMV前24小时将超免疫MCMV血清被动转移给患有MAIDS的小鼠时,未能降低眼内MCMV滴度、视网膜炎频率或视网膜炎严重程度。接受正常小鼠血清并视网膜下注射MCMV的MAIDS动物的全眼,其眼内MCMV滴度为4.3 log10,视网膜炎频率为89%(严重程度评分=55%),而接受抗体治疗的患有MAIDS的小鼠的全眼,其眼内MCMV滴度为4.3 log10,视网膜炎频率为87%(严重程度评分=57%)。在视网膜下接种MCMV前给予患有MAIDS的小鼠中和性MCMV特异性单克隆抗体的被动转移,也未能降低MCMV视网膜炎的频率或严重程度。我们的研究结果表明,单独的抗体免疫疗法对艾滋病患者的巨细胞病毒性视网膜炎治疗无效。