Ultra-violet irradiation and riboflavin treatment blocks capping of cellular adhesion molecules and abrogates immunogenicity of antigen presenting cells (P1388)

Abstract

Abstract UV light has known immunomodulatory activity and is used in clinical situations such as for psoriasis. Mirasol treatment, a pathogen reduction technology based on ultra-violet light irradiation in the presence of riboflavin (UV+R), suppresses the ability of treated WBCs to stimulate proliferation of allogeneic T cells in vitro. Prior work showed that surface expression of adhesion molecules was down-regulated after UV+R treatment. We now show that, UV+ R treatment also decreased capping of the intercellular adhesion molecules (ICAMs)-1, -2, -3 and lymphocyte function-associated antigen (LFA)-3. UV+R treated U937 antigen presenting cells (APCs) induce decreased cell-cell conjugation with PBMCs 25% (p = 0.003) and show a 66% (p = 0.0005) reduction in stimulating T cell proliferation in a mixed lymphocyte reaction compared to untreated or gamma-irradiated U937 APCs. Additionally, UV+R treated U937 APCs failed to induce expression of the early T cell activation marker CD69 and also have decreased membrane viscosity when compared to untreated APCs. Diminished surface expression and perturbation of adhesion receptors within the U937 APCs plasma membrane down-regulates T cell stimulation and proliferation in vitro by lowering the surface expression of adhesion receptors needed for cell-cell conjugation and by perturbation of the ability to mobilize and aggregate adhesion receptors to form a cap, a critical component needed for T cell activation.