In vitro kinetic analysis of cellular anti-MUC1 immune responses in MUC1 transgenic mice

A C57B16 human MUC1 transgenic (MUC1Tg) mouse model has been developed to evaluate immunity and tolerance to MUC1. MUC1Tg mice develop progressively growing tumors when challenged with MUC1-expressing B16 cells. In contrast, non-transgenic (nonTg) mice rejected the tumor or developed tumors that progressed at significantly slower rates. The time course in which both MUC1-specific and tumor specific cellular immune responses developed were evaluated by a modified CTLp limiting dilution assay. In MUC1Tg mice, anti-MUC1 CTL responses peaked at day 20 post tumor challenge and declined rapidly by day 25. In contrast, the anti-MUC1 response peaked at day 25, but at a lower level in nonTg mice. Levels of non-MUC1 directed tumor specific responses were similar initially, but decreased by day 25 in MUC1Tg mice. In contrast, in nonTg mice, tumor specific responses peaked at day 20 and declined by day 25 and 34. NonTg mice were adoptively transferred with primed nonTg lymphocytes and then rechallenged with MUC1-expressing tumors. These mice have higher levels of MUC1 specific CTLp at day 20 post tumor challenge than non transferred nonTg mice, but the CTLp frequency decreases by day 34 post tumor challenge. In contrast, the tumor specific response increased slowly to day 20 and peaked at day 34 post tumor challenge. These in vitro data suggest that MUC1Tg mice do not delete all MUC1 specific CTL during thymic development. It remains to be determined why these CTL are not sufficient to provide tumor protection.