Okabayashi M, Angell M G, Christensen N D, Kreider J W
Department of Pathology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Int J Cancer. 1991 Dec 2;49(6):919-23. doi: 10.1002/ijc.2910490620.
Spontaneous regressions of papillomavirus lesions frequently occur in both human and animal infections. The mechanism by which this occurs is currently unknown. Mononuclear infiltrates are found in regressing human and rabbit papillomas. To assess the potential functional role of these infiltrates in regression, we have characterized and quantitated the cell types present in regressing rabbit lesions. Forty New Zealand white rabbits were inoculated with cottontail rabbit papillomavirus (CRPV) at 2 sites on the dorsal skin. All tumors on 6 rabbits markedly decreased in volume within 6 to 8 weeks of inoculation. Tumors on 4 of these 6 regressor rabbits were studied by immunohistochemistry. Regressor papillomas had conspicuous leucocytic infiltrates, most concentrated at the epithelial basement membrane, and often obliterating the basal cells of the germinal layer. Infiltrating leucocytes were also concentrated in the subjacent dermis immediately beneath the basement membrane. The infiltrates gradually lessened at increased depths in the dermis. In contrast, progressor papillomas contained fewer leucocytes, which were randomly distributed in the dermis. The phenotype of the infiltrating leucocytes was examined in 4 regressing and 12 progressing papillomas. In regressing papillomas, infiltrating leucocytes were predominantly T cells (68.0%), with relatively few B cells (7.4%). Progressing papilloma dermis contained fewer T cells and B cells than regressing papillomas. Most of the infiltrating T cells in regressing papillomas were labelled with a rabbit MHC-class-II-specific monoclonal antibody (MAb) (2C4), in contrast to only a small number in progressing papillomas. In addition to the leucocytic infiltrates, keratinocytes in regressing, but not in progressing, papillomas, frequently exhibited strong 2C4 staining. These results demonstrate that infiltration with T cells expressing rabbit class II is characteristic of regressing Shope papillomas and strengthens the assertion that cell-mediated immunity is the mechanism of Shope papilloma regression.
乳头瘤病毒损伤的自发消退在人类和动物感染中均经常发生。其发生机制目前尚不清楚。在消退期的人类和兔乳头瘤中可发现单核浸润。为评估这些浸润在消退过程中的潜在功能作用，我们已对消退期兔损伤中存在的细胞类型进行了特征描述和定量分析。40只新西兰白兔在背部皮肤的2个部位接种了棉尾兔乳头瘤病毒（CRPV）。接种后6至8周内，6只兔子身上的所有肿瘤体积均显著减小。对这6只消退期兔子中4只的肿瘤进行了免疫组织化学研究。消退期乳头瘤有明显的白细胞浸润，大部分集中在上皮基底膜处，常使生发层的基底细胞消失。浸润的白细胞也集中在基底膜下方紧邻的真皮层。随着真皮层深度增加，浸润逐渐减少。相比之下，进展期乳头瘤中的白细胞较少，随机分布在真皮层。在4个消退期和12个进展期乳头瘤中检查了浸润白细胞的表型。在消退期乳头瘤中，浸润的白细胞主要是T细胞（68.0%），B细胞相对较少（7.4%）。进展期乳头瘤真皮层中的T细胞和B细胞比消退期乳头瘤少。与进展期乳头瘤中只有少量T细胞被标记不同，消退期乳头瘤中大多数浸润T细胞被兔MHC-II类特异性单克隆抗体（MAb）（2C4）标记。除白细胞浸润外，消退期乳头瘤中的角质形成细胞（而非进展期乳头瘤中的角质形成细胞）常表现出强烈的2C4染色。这些结果表明，表达兔II类分子的T细胞浸润是消退期肖普乳头瘤的特征，并强化了细胞介导免疫是肖普乳头瘤消退机制的观点。
