PHENOTYPICAL CHARACTERIZATION OF LYMPHOCYTES INFILTRATING REGRESSING PAPILLOMAS

Papillomavirus-induced lesions often regress spontaneously in both hum ans and animals, Papilloma regression is deemed to be due to a cell-me diated 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 papi llomas, we have analyzed biopsies of papillomas induced in the soft pa late of cattle by bovine papillomavirus type 4 (BPV-4) and have phenot ypically 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 lymphocyte s in the subepithelial derma of papillomas but not in normal palate ti ssue; these cellular masses consisted predominantly of CD4(+) lymphocy tes, with only a few CD8(+) and gamma delta(WC1(+)) lymphocytes, gener ally positioned at the periphery of these masses, All three subtypes o f lymphocytes were found interdigitated with the cells of the basal la yer both in papillomas and in normal palate tissue, but while basal la yer 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 papi llomas, but the CD8(+) and gamma delta(WC1(+)) T cells were more numer ous 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 C D4(+) lymphocytes are specifically and massively recruited into the re gressing papillomas, and that although all three lymphocyte subsets ca n penetrate the papilloma, only the CD8(+) and gamma delta(WC1(+)) lym phocytes are able to migrate into the fronds, These results suggest th at all three lymphocyte subsets have an important role to fulfill duri ng natural regression of papillomas.