Kadima-Nzuji M, Craighead J E
Department of Pathology, University of Vermont, College of Medicine, Burlington 05405.
Am J Pathol. 1990 Oct;137(4):907-12.
Cytomegalovirus (CMV) infections were induced in male BALB/c mice treated with rat monoclonal antibodies (MAb) to deplete selectively CD8 and CD4 cell populations in vivo. The animals were then inoculated intraperitoneally with murine CMV and the infection was monitored virologically and histologically. High concentrations of virus were found in the lungs of mice depleted of CD4 or both CD4 and CD8 cells. These animals developed pulmonary infections that persisted for at least 49 days after inoculation. In contrast, immunologically intact mice and those administered anti-CD8 MAb experienced only a transient infection of the lungs. Focal interstitial infiltrates of mononuclear cells were demonstrated in pulmonary tissues of CD4 MAb-treated animals, but not in normal mice and those receiving the CD8 MAb. Adoptive transfer of CD4 cells to animals (rendered immune-incompetent by thymectomy and irradiation) protected against pulmonary infection and the development of interstitial pneumonia. Mice treated with CD4 MAb failed to produce specific CMV antibody, whereas the depletion of CD8 cells had no effect on antibody elaboration. Administration of anti-CD4 and CD8 MAb did not affect virus replication in the salivary glands, the preferential site for CMV infection in the mouse. Induction of pulmonary infection and interstitial pneumonia by CMV in BALB/c mice is mediated by CD4 T cells.
用大鼠单克隆抗体(MAb)处理雄性BALB/c小鼠,以在体内选择性耗竭CD8和CD4细胞群,从而诱导巨细胞病毒(CMV)感染。然后给这些动物腹腔接种鼠巨细胞病毒,并通过病毒学和组织学方法监测感染情况。在耗竭CD4细胞或同时耗竭CD4和CD8细胞的小鼠肺中发现了高浓度病毒。这些动物发生了肺部感染,接种后至少持续49天。相比之下,免疫功能完整的小鼠和给予抗CD8单克隆抗体的小鼠仅经历了短暂的肺部感染。在接受CD4单克隆抗体处理的动物的肺组织中发现了单核细胞的局灶性间质浸润,而正常小鼠和接受CD8单克隆抗体的小鼠则未发现。将CD4细胞过继转移到动物(通过胸腺切除和照射使其免疫无能)可预防肺部感染和间质性肺炎的发生。用CD4单克隆抗体处理的小鼠未能产生特异性CMV抗体,而耗竭CD8细胞对抗体产生没有影响。给予抗CD4和抗CD8单克隆抗体不影响唾液腺中的病毒复制,唾液腺是小鼠中CMV感染的优先部位。BALB/c小鼠中CMV诱导的肺部感染和间质性肺炎是由CD4 T细胞介导的。