Knowles G, O'Neil B W, Campo M S
The Beatson Institute for Cancer Research, CRC Beatson Laboratories, Bearsden, Glasgow, Scotland, United Kingdom.
J Virol. 1996 Dec;70(12):8451-8. doi: 10.1128/JVI.70.12.8451-8458.1996.
Papillomavirus-induced lesions often regress spontaneously in both humans and animals. Papilloma regression is deemed to be due to a cell-mediated immune response, the nature of which is still ill defined, and is accompanied by immune cell infiltrates. To gain further information on the nature and role of the immune cells present in regressing papillomas, we have analyzed biopsies of papillomas induced in the soft palate of cattle by bovine papillomavirus type 4 (BPV-4) and have phenotypically characterized and quantified the lymphocytes present in these lesions. Eleven papilloma biopsies and seven biopsies of noninfected palate were analyzed for the presence of activated CD4+, CD8+, and gamma delta(WC1+) lymphocytes. We found large numbers of lymphocytes in the subepithelial derma of papillomas but not in normal palate tissue; these cellular masses consisted predominantly of CD4+ lymphocytes, with only a few CD8+ and gamma delta(WC1+) lymphocytes, generally positioned at the periphery of these masses. All three subtypes of lymphocytes were found interdigitated with the cells of the basal layer both in papillomas and in normal palate tissue, but while basal layer CD8+ and gamma delta(WC1+) T cells were detected with similar frequencies in papillomas and uninfected palate, basal layer CD4+ T cells were much more frequent in papillomas. CD4+, CD8+, and gamma delta(WC1+) lymphocytes were found in the suprabasal layers of papillomas, but the CD8+ and gamma delta(WC1+) T cells were more numerous and had migrated further into the differentiating keratinocytes of the papilloma fronds than the CD4+ T cells. We conclude that T-cell infiltration is characteristic of regressing BPV-4 papillomas, that CD4+ lymphocytes are specifically and massively recruited into the regressing papillomas, and that although all three lymphocyte subsets can penetrate the papilloma, only the CD8+ and gamma delta(WC1+) lymphocytes are able to migrate into the fronds. These results suggest that all three lymphocyte subsets have an important role to fulfill during natural regression of papillomas.
乳头瘤病毒引起的病变在人类和动物中常常会自发消退。乳头瘤消退被认为是由于细胞介导的免疫反应，但其本质仍不清楚，且伴有免疫细胞浸润。为了进一步了解消退期乳头瘤中存在的免疫细胞的性质和作用，我们分析了牛乳头瘤病毒4型（BPV - 4）诱导的牛软腭乳头瘤的活检样本，并对这些病变中存在的淋巴细胞进行了表型特征分析和定量。对11份乳头瘤活检样本和7份未感染软腭的活检样本进行分析，以检测活化的CD4 +、CD8 +和γδ（WC1 +）淋巴细胞的存在情况。我们发现乳头瘤的上皮下真皮中有大量淋巴细胞，而正常软腭组织中则没有；这些细胞团主要由CD4 +淋巴细胞组成，只有少数CD8 +和γδ（WC1 +）淋巴细胞，通常位于这些细胞团的周边。在乳头瘤和正常软腭组织中，均发现所有三种淋巴细胞亚型与基底层细胞相互交错，但虽然在乳头瘤和未感染的软腭中检测到基底层CD8 +和γδ（WC1 +）T细胞的频率相似，但基底层CD4 + T细胞在乳头瘤中更为常见。在乳头瘤的基底层上层发现了CD4 +、CD8 +和γδ（WC1 +）淋巴细胞，但与CD4 + T细胞相比，CD8 +和γδ（WC1 +）T细胞数量更多，并且已进一步迁移到乳头瘤叶状突起的分化角质形成细胞中。我们得出结论，T细胞浸润是消退期BPV - 4乳头瘤的特征，CD4 +淋巴细胞被特异性大量募集到消退期乳头瘤中，并且虽然所有三种淋巴细胞亚群都能穿透乳头瘤，但只有CD8 +和γδ（WC1 +）淋巴细胞能够迁移到叶状突起中。这些结果表明，所有三种淋巴细胞亚群在乳头瘤自然消退过程中都发挥着重要作用。
