title: MUC1 mucin is expressed on human T-regulatory cells: function in both co-stimulation and co-inhibition.
abstract: 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.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Konowalchuk
authors.forename: Babita
authors.initials: B
authors.lastname: Agrawal
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: D017252:CD3 Complex; D060889:Inducible T-Cell Co-Stimulator Protein; C060192:MUC1 protein, human; D018396:Mucin-1