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

Takemasa Tsuji; Junko Matsuzaki; Erika Ritter; Anthony Miliotto; Gerd Ritter; Kunle Odunsi; Lloyd J Old; Sacha Gnjatic

doi:10.1371/journal.pone.0023651

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

PLoS One. 2011;6(8):e23651. doi: 10.1371/journal.pone.0023651. Epub 2011 Aug 12.

Authors

Takemasa Tsuji¹, Junko Matsuzaki, Erika Ritter, Anthony Miliotto, Gerd Ritter, Kunle Odunsi, Lloyd J Old, Sacha Gnjatic

Affiliation

¹ Ludwig Institute for Cancer Research Ltd., New York Branch at Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Antigens, Neoplasm / immunology*
Antigens, Neoplasm / metabolism
Autoantibodies / blood
Autoantibodies / immunology
Autoantigens / immunology*
Autoantigens / metabolism
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / metabolism
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Epitopes, T-Lymphocyte / immunology
Epitopes, T-Lymphocyte / metabolism
Female
Humans
Immune Tolerance / immunology*
Immunoglobulin G / blood
Immunoglobulin G / immunology
Interferon-gamma / immunology
Interferon-gamma / metabolism
Leukocyte Common Antigens / immunology
Leukocyte Common Antigens / metabolism
Male
Membrane Proteins / immunology
Membrane Proteins / metabolism
Molecular Sequence Data
Mutation
Ovarian Neoplasms / immunology
Ovarian Neoplasms / metabolism
Ovarian Neoplasms / pathology
Peptides / genetics
Peptides / immunology
Peptides / metabolism
T-Lymphocytes / immunology*
T-Lymphocytes / metabolism
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / immunology
Tumor Suppressor Protein p53 / metabolism

Substances

Antigens, Neoplasm
Autoantibodies
Autoantigens
CTAG1B protein, human
Epitopes, T-Lymphocyte
Immunoglobulin G
Membrane Proteins
Peptides
Tumor Suppressor Protein p53
Interferon-gamma
Leukocyte Common Antigens