Wünschmann A, Alldinger S, Kremmer E, Baumgärtner W
Institut für Veterinär-Pathologie, Justus-Liebig-Universität, Giessen, Germany.
Vet Immunol Immunopathol. 1999 Feb 1;67(2):101-16. doi: 10.1016/s0165-2427(98)00216-5.
CD4 and CD8 antigen expression of T cells as well as B cell and canine distemper virus (CDV) antigen distribution were immunohistologically examined in the cerebellum of dogs with spontaneous distemper encephalitis. Cellular and viral antigen expression were evaluated at intralesional and extralesional sites and in the perivascular space. Histologically, acute and subacute non-inflammatory encephalitis and subacute inflammatory and chronic plaques were distinguished. Demyelination was a feature of all subacute and chronic lesions, although the majority of plaques exhibited no or only a low level of active demyelination as demonstrated by single macrophages with luxol fast blue positive material in their cytoplasm. CDV antigen expression, observed in all distemper brains, was reduced in chronic plaques. CD4+, CD8+, and B cells were absent in controls and in some brains with acute encephalitis. A mild infiltration of CD8+ cells was noticed in the neuropil of the remaining brains with acute and all brains with subacute non-inflammatory encephalitis. Single CD4+ cells were found in two brains with acute and in all brains with subacute non-inflammatory encephalitis. Numerous CD8+ and CD4+ cells and few B cells, with a preponderance of CD8+ cells, were detected in subacute inflammatory and chronic lesions. In contrast, in perivascular infiltrates (PVI) of subacute and chronic lesions a dominance of CD4+ cells was detected. The dominating CD8+ cells in acute and subacute non-inflammatory encephalitis might be involved in viral clearance or contribute as antibody-independent cytotoxic T cells to early lesion development. In subacute inflammatory and chronic lesions CD8+ cells may function as cytotoxic effector cells and CD4+ cells by initiating a delayed-type hypersensitivity reaction. The simultaneous occurrence of perivascular B and CD4+ cells indicated that an antibody-mediated cytotoxicity could synergistically enhance demyelination. Summarized, temporal and spatial distribution of CD4+, CD8+ and B cells and virus antigen in early and late lesions support the hypothesis of a heterogeneous in part immune-mediated plaque pathogenesis in distemper demyelination.
对患有自发性犬瘟热脑炎的犬小脑进行免疫组织学检查，以观察T细胞的CD4和CD8抗原表达以及B细胞和犬瘟热病毒（CDV）抗原分布。在病灶内和病灶外部位以及血管周围间隙评估细胞和病毒抗原表达。组织学上，区分出急性和亚急性非炎性脑炎以及亚急性炎性和慢性斑块。脱髓鞘是所有亚急性和慢性病变的一个特征，尽管大多数斑块表现为无活性脱髓鞘或仅有低水平的活性脱髓鞘，如单个巨噬细胞胞质内有卢氏快蓝阳性物质所示。在所有犬瘟热脑病中均观察到CDV抗原表达，在慢性斑块中其表达减少。对照组以及一些患有急性脑炎的大脑中不存在CD4 +、CD8 +和B细胞。在其余患有急性脑炎的大脑以及所有患有亚急性非炎性脑炎的大脑的神经纤维网中，注意到有轻度的CD8 +细胞浸润。在两个患有急性脑炎的大脑以及所有患有亚急性非炎性脑炎的大脑中发现了单个CD4 +细胞。在亚急性炎性和慢性病变中检测到大量CD8 +和CD4 +细胞以及少量B细胞，其中CD8 +细胞占优势。相比之下，在亚急性和慢性病变的血管周围浸润（PVI）中检测到CD4 +细胞占优势。急性和亚急性非炎性脑炎中占主导的CD8 +细胞可能参与病毒清除，或作为非抗体依赖性细胞毒性T细胞促进早期病变发展。在亚急性炎性和慢性病变中，CD8 +细胞可能作为细胞毒性效应细胞发挥作用，而CD4 +细胞则通过引发迟发型超敏反应发挥作用。血管周围B细胞和CD4 +细胞同时出现表明抗体介导的细胞毒性可能协同增强脱髓鞘作用。总之，CD4 +、CD8 +和B细胞以及病毒抗原在早期和晚期病变中的时空分布支持了犬瘟热脱髓鞘中部分免疫介导的斑块发病机制具有异质性这一假说。
