Bigger J E, Tanigawa M, Thomas C A, Atherton S S
Department of Microbiology, The University of Texas Health Science Center at San Antonio, 78229,USA.
Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2608-13.
Human cytomegalovirus retinitis, the most common ophthalmic infection of AIDS patients, has been modeled in BALB/c mice infected with murine cytomegalovirus by the supraciliary route. A series of depletion and adoptive transfer studies was performed to determine whether adoptive transfer of T cells protects mice from retinitis caused by murine cytomegalovirus infection after supraciliary inoculation and to determine which subset of T cells is responsible for protection.
BALB/c mice were thymectomized and T cell-depleted by injection of monoclonal antibodies to CD4, CD8, or both. Murine cytomegalovirus (9 x 10(2) plaque forming units [pfu]) was injected into the supraciliary space. Experimental animals received murine cytomegalovirus-specific T cells or subsets of T cells 2 hours before virus injection, whereas control animals received herpes simplex virus type 1-specific T cells by tail vein injection. Eight days after virus injection, retinal pathology was scored by histopathologic examination of hematoxylin and eosin-stained ocular sections.
CD8+ T cell depletion was sufficient for development of retinitis after supraciliary injection of murine cytomegalovirus. Adoptive transfer of murine cytomegalovirus-specific T cells, but not herpes simplex virus type 1-specific T cells, provided protection from retinitis. Additionally, separation of the murine cytomegalovirus-specific T cells into CD8+ and CD4+ subsets before adoptive transfer showed that the CD8+ fraction of the adoptive T cells was responsible for protection.
These results suggest that adoptive transfer of cytomegalovirus-specific T cells or T cell subsets might be used to treat or prevent cytomegalovirus retinitis in immunosuppressed human patients.
人类巨细胞病毒性视网膜炎是艾滋病患者最常见的眼部感染，已通过经睫状体上腔途径感染鼠巨细胞病毒的BALB/c小鼠建立了模型。进行了一系列的细胞耗竭和过继转移研究，以确定T细胞的过继转移是否能保护小鼠免受经睫状体上腔接种鼠巨细胞病毒引起的视网膜炎，并确定哪种T细胞亚群负责这种保护作用。
对BALB/c小鼠进行胸腺切除，并通过注射抗CD4、抗CD8或两者的单克隆抗体使T细胞耗竭。将鼠巨细胞病毒（9×10² 空斑形成单位 [pfu]）注入睫状体上腔。实验动物在病毒注射前2小时接受鼠巨细胞病毒特异性T细胞或T细胞亚群，而对照动物通过尾静脉注射1型单纯疱疹病毒特异性T细胞。病毒注射8天后，通过苏木精和伊红染色的眼部切片的组织病理学检查对视网膜病理学进行评分。
经睫状体上腔注射鼠巨细胞病毒后，CD8⁺ T细胞耗竭足以导致视网膜炎的发生。鼠巨细胞病毒特异性T细胞的过继转移，而非1型单纯疱疹病毒特异性T细胞，提供了对视网膜炎的保护。此外，在过继转移前将鼠巨细胞病毒特异性T细胞分离为CD8⁺ 和CD4⁺ 亚群表明，过继T细胞的CD8⁺ 部分负责这种保护作用。
这些结果表明，巨细胞病毒特异性T细胞或T细胞亚群的过继转移可能用于治疗或预防免疫抑制的人类患者的巨细胞病毒性视网膜炎。
