ABSTRACT
Cervical cancer is the possible outcome of a genital infection with high-risk human papillomavirus type 16 (HPV16) and is preceded by a phase of persistent HPV infection during which the host immune system fails to eliminate the virus. Our previous work showed that failure is reflected by the absence of type 1 T-cell immunity against HPV16 early antigens E2 and E6 in patients with HPV16+ cervical lesions. We now show that a majority of both patients with cervical lesions and healthy subjects display HPV16 L1 peptide-specific type 1 T-cell responses with similar magnitude. The T-cell response in patients was directed at a broad range of peptides within L1, suggesting that during persistent or repeated exposure to HPV16 L1, the immune system maximizes its efforts to counter the viral challenge. Unlike the type 1 T-cell responses against HPV16 early antigens E2 and E6, type 1 T-cell immunity against L1 does not correlate with health or disease. This argues that T-cell responses against early and late HPV16 antigens essentially differ in the manner in which they are induced and regulated, as well as in their impact on the subsequent stages of HPV16-induced cervical disease.
Subject(s)
Capsid Proteins/immunology , DNA-Binding Proteins/immunology , Oncogene Proteins, Viral/immunology , Papillomavirus Infections/immunology , Repressor Proteins/immunology , T-Lymphocytes/immunology , Uterine Cervical Dysplasia/immunology , Uterine Cervical Neoplasms/immunology , Adult , Aged , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Female , Humans , Immunity, Cellular , Interferon-gamma/metabolism , Middle Aged , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology , Uterine Cervical Dysplasia/virologyABSTRACT
SJL mice immunized with mannosylated (M-) PLP(139-151) in complete adjuvant do not develop EAE and little CNS mononuclear cell infiltration; other mannosylated peptides were ineffective in this experimental setting. Despite apparently normal T cell responses, M-PLP(139-151)-immunized mice show impaired delayed-type-sensitivity to PLP(139-151) but a normal response to other peptides. After re-immunization with PLP(139-151) in complete adjuvant, these mice are largely tolerant to EAE, show less T cell proliferation and decreased peptide-specific IgG2a. Our data suggest that M-PLP(139-151) induces peptide-specific tolerance to EAE via a mechanism of deletion or impaired migration of encephalitogenic T cells.
