Characterization of T cell ligands for uromodulin: a possible role in costimulation.

In this study, we demonstrate that uromodulin (UMN) is a costimulator of T cells and characterize the T cell ligand which might mediate its costimulatory effect. UMN is an 85-kDa human urinary glycoprotein which is better known for its ability to suppress antigen-induced proliferation of peripheral blood mononuclear cells. It also has a mitogenic effect on peripheral blood cells, which has not been investigated.

In vitro cell aggregation and cell adhesion molecules in Crohn's disease.

Background: Lack of a suitable model has hindered efforts to understand inflammation and granuloma formation in Crohn's disease.

Methods: Granulomalike aggregates of circulating mononuclear cells are produced in vitro by cultures of cells with polyacrylamide beads. To identify features of in vitro aggregates, which are similar to tissue granulomas of Crohn's disease, the gross morphology and immunohistological appearance of the aggregates produced with peripheral blood mononuclear cells from patients with Crohn's disease were analyzed, and the size of in vitro aggregates was correlated with clinical activity of the disease.

Evidence that specific high mannose structures directly regulate multiple cellular activities.

Previous studies have demonstrated that much of the immunomodulatory activity of the glycoprotein uromodulin can be attributed to attached oligosaccharides. Structural studies of isolated and purified saccharides derived from uromodulin suggest that the structure Man6GlcNAc2-asn can inhibit in vitro assays of antigen driven T cell proliferation. Based on these observations, we isolated a series of high mannose glycopeptides from a variety of natural sources and tested them for biological activity in a number of assays.

Uromodulin: a specific inhibitor of IL-1-initiated human T cell colony formation.

Uromodulin, an 85 kDa naturally occurring immunosuppressant, was found to selectively and specifically inhibit the ability of IL-1 to induce colony responses by highly enriched suspensions of PHA-stimulated T lymphocytes. Dilutions of 1 x 10(-8) M completely blocked the colony growth of T lymphocytes cultured with 50 U/ml IL-1; 1 x 10(-9) M dilutions reduced scores by 83%. By contrast, uromodulin did not inhibit the responses of unseparated mononuclear cells, isolated T lymphocytes cultured with irradiated adherent cells, or stimulated T cells whose growth was initiated by either IL-2 or a soluble factor derived from Raji cells.