title: Split T cell tolerance against a self/tumor antigen: spontaneous CD4+ but not CD8+ T cell responses against p53 in cancer patients and healthy donors.
abstract: Analyses of NY-ESO-1-specific spontaneous immune responses in cancer patients revealed that antibody and both CD4(+) and CD8(+) T cell responses were induced together in cancer patients. To explore whether such integrated immune responses are also spontaneously induced for other tumor antigens, we have evaluated antibody and T cell responses against self/tumor antigen p53 in ovarian cancer patients and healthy individuals. We found that 21% (64/298) of ovarian cancer patients but no healthy donors showed specific IgG responses against wild-type p53 protein. While none of 12 patients with high titer p53 antibody showed spontaneous p53-specific CD8(+) T cell responses following a single in vitro sensitization, significant p53-specific IFN-γ producing CD4(+) T cells were detected in 6 patients. Surprisingly, similar levels of p53-specific CD4(+) T cells but not CD8(+) T cells were also detected in 5/10 seronegative cancer patients and 9/12 healthy donors. Importantly, p53-specific CD4(+) T cells in healthy donors originated from a CD45RA(-) antigen-experienced T cell population and recognized naturally processed wild-type p53 protein. These results raise the possibility that p53-specific CD4(+) T cells reflect abnormalities in p53 occurring in normal individuals and that they may play a role in processes of immunosurveillance or immunoregulation of p53-related neoplastic events.
authors.affiliation: Ludwig Institute for Cancer Research Ltd., New York Branch at Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Takemasa
authors.initials: T
authors.lastname: Tsuji
authors.forename: Junko
authors.initials: J
authors.lastname: Matsuzaki
authors.forename: Erika
authors.initials: E
authors.lastname: Ritter
authors.forename: Anthony
authors.initials: A
authors.lastname: Miliotto
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D001324:Autoantigens; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D008565:Membrane Proteins; D010455:Peptides; D016159:Tumor Suppressor Protein p53; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens