HUMAN PAPILLOMAVIRUS-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN PATIENTS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA GRADE III

Human papillomaviruses (HPVs), especially types 16 and 18, are strongl y associated with the development of cervical intraepithelial neoplasi a (GIN) and invasive carcinoma, The HPV E6 and E7 proteins are express ed constitutively in the majority of CIN lesions and carcinomas. There fore, they are targets for the immune response against HPV and candida tes for active immunotherapy, We have previously detected HPV-specific CTLs from the peripheral blood mononuclear cells from a cervical canc er patient following immunization with a recombinant vaccinia using in vitro restimulation with adenovirus recombinants expressing HPV16 or HPV18 E6/E7 fusion proteins, In this study, we used a similar protocol to determine the prevalence of CTL responses against HPV16 and HPV18 E6/E7 in the peripheral blood mononuclear cells from 10 CIN Hi and 10 normal subjects, HPV-specific CTL responses were detected in 6 of 10 C IN III subjects, These CTL lines recognized HPV16 E6/E7 proteins prese nted by at Least three MHC class 1 HLA alleles and by HPV-transformed CaSki cells, No HPV-specific CTLs were detected in normal subjects, Th is study demonstrates the presence of naturally occurring HPV-specific memory CTLs in a majority of CIN III patients and provides an approac h for further study of their role in modulating cervical malignancy.