Tolerance and immunity to MUC1 in a human MUC1 transgenic murine model

C57BL/6 mice transgenic for the human tumor associated antigen MUC1 (MUC1 Tg) have been produced to investigate the effect of endogenous expression of MUC1 on immunity and tolerance to MUC1. Cellular adoptive transfer techniques were used to evaluate MUC1 tumor immunity in vivo. Immune cells from non-Tg or MUC1 Tg mice challenged with MUC1⁺ syngeneic B16 tumors were adoptively transferred to non-Tg recipients. Recipient or control non-Tg mice were then challenged with MUC1⁺ or control syngeneic B16 cells and rates of tumor growth were compared between recipient and control non-Tg mice as an indication of tumor immunity transfer. The results of these studies revealed that i) MUC1 is the dominant tumor antigen in non-Tg mice: ii) non-Tg MUC1 tumor immunity is acquired, maintained and undectable at week 7 post-tumor challenge; and iii) MUC1 Tg mice are tolerant to MUC1. Enriched CD4⁺ but not CD8⁺ lymphocytes from non-Tg mice challenged with MUC1⁺ syngeneic B16 cells were capable of transferring MUC1 tumor immunity to non-Tg recipients. Additionally, antibody-mediated depletion of CD4⁺ but not CD8⁺ cells in vivo resulted in the loss of MUC1 tumor immunity in non-Tg mice. Whereas significant MUC1 tumor immunity could be adoptively transferred to non-Tg recipients, only modest MUC1 tumor immunity could be transferred to MUC1 Tg recipients. No detectable autoimmunity was observed in tissues expressing MUC1 in the latter group of mice.