title: Resolution of cervical dysplasia is associated with T-cell proliferative responses to human papillomavirus type 16 E2.
abstract: The 'high-risk' human papillomaviruses (HPVs) cause persistent infections of the anogenital region that may resolve spontaneously following activation of a protective immune response. The aim of this study was to determine whether cell-mediated immunity (CMI) to the early protein E2 was associated with disease regression and to establish whether E2 CMI and antibodies to L1 virus-like particles (VLPs) were associated markers of immunity to HPV. Lymphoproliferative responses to histidine-tagged E2 and antibody responses to VLPs were measured in patients with persistent cervical dysplasia, those whose disease had recently resolved and normal controls. Resolvers had significantly higher E2-specific lymphoproliferative responses when compared with normal controls or persisters, whereas there was no significant difference between the persisters and the normal controls. The T cells stimulated by E2 secreted high levels of gamma interferon (IFN-gamma), consistent with a type 1 helper (Th1) phenotype. VLP IgG responses were associated with current or previous HPV infection, but not with disease regression or a lymphoproliferative response to E2. Major histocompatibility complex class I-restricted T cells secreted IFN-gamma following stimulation with E1, and E2 peptides were detected more frequently in the persister group. The data showed that lymphoproliferative responses to E2 with a cytokine profile indicative of Th1 are associated with disease resolution, supporting the development of a therapeutic vaccine that activates this type of response for the treatment of individuals with pre-existing disease.
authors.affiliation: Virus Research Unit, Dept Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dillon
authors.affiliation: Faculty of Medicine, Kanazawa University, Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sasagawa
authors.affiliation: Virus Research Unit, Dept Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: Anna
authors.initials: A
authors.lastname: Crawford
authors.affiliation: Student Health Services, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: Jan
authors.initials: J
authors.lastname: Prestidge
authors.affiliation: Virus Research Unit, Dept Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: Marie K
authors.initials: MK
authors.lastname: Inder
authors.affiliation: Student Health Services, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: Jim
authors.initials: J
authors.lastname: Jerram
authors.affiliation: Virus Research Unit, Dept Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Mercer
authors.affiliation: Virus Research Unit, Dept Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: Merilyn
authors.initials: M
authors.lastname: Hibma
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D036022:Capsid Proteins / Q000276:immunology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D015395:Histocompatibility Antigens Class I; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16; D007371:Interferon-gamma