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.

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-c 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. [ABSTRACT FROM AUTHOR]