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.