Lu Y, Bigger J E, Thomas C A, Atherton S S
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio 78284, USA.
Invest Ophthalmol Vis Sci. 1997 Feb;38(2):301-10.
The purpose of this study was to determine whether adoptive transfer of murine cytomegalovirus (MCMV)-immune lymph node cells prevents retinitis in immunosuppressed mice.
Adult BALB/c mice were thymectomized and T-cell depleted using rat monoclonal antibodies specific for mouse CD4+ and CD8+ T-cells. The level of rat immunoglobulin G in the treated mice was monitored by enzyme-linked immunosorbent assay. Immune cells were labeled with PKH26-GH immediately before adoptive transfer, and flow cytometry was used to determine the percentage of adoptively transferred T-cells (PKH+, fluorescein isothiocyanate [FITC+]) in the spleens of the recipient mice 3 days after transfer. The ability of adoptively transferred cells to protect from retinitis was studied in T-cell-depleted mice injected with MCMV through the supraciliary route. Mice received 4 x 10(7) in vitro-restimulated MCMV-immune cells, 4 x 10(7) freshly isolated MCMV-immune cells, 4 x 10(7) freshly isolated ovalbumin-immune cells, or no cells (control group).
The best time to balance depletion of endogenous T-cells with persistence of transferred cells was 3 weeks after T-cell depletion. Both restimulated and freshly isolated MCMV-immune cells conferred protection from retinitis. Freshly isolated ovalbumin-immune lymph node cells did not prevent retinitis, indicating that protection was virus-specific and merely was not because of transfer of antigen-activated lymph node cells.
Adoptive immunotherapy has been used to prevent cytomegalovirus (CMV) infection in patients who have undergone transplantation, and, by extrapolation, the results of these studies suggest that adoptive immunotherapy with human CMV-specific immune cells might be used to prevent or ameliorate CMV retinitis in immunocompromised patients.
本研究旨在确定过继转移鼠巨细胞病毒（MCMV）免疫的淋巴结细胞是否能预防免疫抑制小鼠的视网膜炎。
成年BALB/c小鼠行胸腺切除术，并使用针对小鼠CD4+和CD8+ T细胞的大鼠单克隆抗体清除T细胞。通过酶联免疫吸附测定法监测处理后小鼠体内大鼠免疫球蛋白G的水平。在过继转移前立即用PKH26-GH标记免疫细胞，并使用流式细胞术测定转移后3天受体小鼠脾脏中过继转移的T细胞（PKH+，异硫氰酸荧光素[FITC+]）的百分比。在通过睫状体上途径注射MCMV的T细胞耗竭小鼠中研究过继转移细胞预防视网膜炎的能力。小鼠接受4×10⁷体外再刺激的MCMV免疫细胞、4×10⁷新鲜分离的MCMV免疫细胞、4×10⁷新鲜分离的卵清蛋白免疫细胞，或不接受细胞（对照组）。
在内源性T细胞耗竭与转移细胞持久性之间取得平衡的最佳时间是T细胞耗竭后3周。再刺激的和新鲜分离的MCMV免疫细胞均能预防视网膜炎。新鲜分离的卵清蛋白免疫淋巴结细胞不能预防视网膜炎，这表明这种保护是病毒特异性的，而不仅仅是由于抗原激活的淋巴结细胞的转移。
过继免疫疗法已被用于预防移植患者的巨细胞病毒（CMV）感染，由此推断，这些研究结果表明，用人CMV特异性免疫细胞进行过继免疫疗法可能用于预防或改善免疫功能低下患者的CMV视网膜炎。
