T cell suppression as a mechanism for tolerance to MUC1 antigen in MUC1 transgenic mice

C57BL/6 mice transgenic for human MUC1 (MUC1.Tg) have been developed to study immunologic responsiveness to the human MUC1 tumor-associated antigen. In the present studies, MUC1.Tg mice were immunized with purified human MUC1 antigen and irradiated MUC1-positive (MC38/MUC1) tumor cells. Immunization with MUC1 antigen was associated with induction of an anti-MUC1 antibody response and no detectable cytotoxic T cell reactivity. Similar findings were obtained after immunization with irradiated MC38/MUC1 tumor cells. The results also demonstrate that immunization of MUC1.Tg mice with MUC1 is associated with decreased levels of CD8+ T cells. In addition, expression of alphabeta T cell receptors and CD28 were down-regulated on CD8+ T cells as a consequence of MUC1 immunization. These findings support a role for T cell suppression in tolerance to MUC1 antigen in MUC1.Tg mice.