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 Journal Article
| Authors: | Tsuji, T.; Matsuzaki, J.; Ritter, E.; Miliotto, A.; Ritter, G.; Odunsi, K.; Old, L. J.; Gnjatic, S. |
| Article 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. © 2011 Tsuji et al. |
| Keywords: | controlled study; human cell; cancer patient; cd8+ t lymphocyte; ovary cancer; in vivo study; in vitro study; protein p53; tumor antigen; cell specificity; immunoregulation; cellular immunity; gamma interferon; immunoglobulin g; ny eso 1 antigen; antibody response; cd4+ t lymphocyte; tumor immunity; cytokine production; immunosurveillance; t lymphocyte activation; sensitization; cd45ra antigen; antibody titer |
| Journal Title: | PLoS ONE |
| Volume: | 6 |
| Issue: | 8 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2011-01-01 |
| Start Page: | e23651 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0023651 |
| PROVIDER: | scopus |
| PMCID: | PMC3155555 |
| PUBMED: | 21858191 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 October 2011" - "Source: Scopus" |
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