MUC1 mucin is expressed on human T-regulatory cells: Function in both co-stimulation and co-inhibition

MUC1 mucin, an important protein of epithelial cells and epithelial-derived carcinomas, is also expressed on activated T cells, showing both positive and negative regulatory functions. It is currently unknown whether MUC1 is a true regulatory protein of T cells and what conditions lead to MUC1 co-stimulation versus co-inhibition. We have found that MUC1 is expressed on the majority of T-regulatory cells (CD4+/CD25+/FoxP3+) in humans (>90%) and that CD3/MUC1 co-stimulation leads to an increased number of T-regulatory cells. We also discovered that the immunoregulatory function is dependent upon the number of accessory (CD3−) cells present, with co-inhibition occurring with <5–10% accessory cells while co-stimulation begins with a reconstitution of ∼50% accessory cells. Co-inhibition was also found to not be the result of the apoptosis but a separate and unknown pathway. This data further characterizes MUC1 as an immunoregulatory protein of T cells capable of giving a positive or negative stimulus.