Dendritic Cells Maturation in Immunosuppressive Agents In Vitro

Abstract

Introduction: The most important antigen-presenting cells (APCs) are dendritic cells (DCs), which present antigen to T cells. The state of maturation of DCs is crucial for induction of a T-cell lymphocyte response. It was noted that immature DCs play an important role in peripheral tolerance, whereas mature DCs induce a complete immune response. We have studied the effect of immunosuppressive agents: rapamycin and cyclosporine A on DC maturation in response to LPS. We have compared their effect when DCs were differentiated in an environment of immunosuppressive agents and then were activated with LPS or they were administered simultaneously with LPS. Methods: Human peripheral blood monocytes were induced by using cytokines: IL-4 and GM-CSF, in the direction of DCs in the presence of rapamycin and cyclosporine A or without drugs. Then the ability of these cells to undergo activation by LPS was evaluated. Additionally, DCs, which had been generated without drugs were activated with LPS simultaneously with rapamycin or cyclosporine A. DCs were identified by the expression of surface molecules: CD11c, HLA-DR (MHC II), CD86 and the absence of CD3, CD4, CD14, CD16, CD19, CD20, CD56 (lin-). Results: We have observed a decrease in the percentage of LPS-activated DC when these cells were differentiated in the presence of immunosuppressive agents. The lowest percentage of DC was noted in an environment of rapamycin. We have also noted a decrease in the percentage of LPS-activated DC when rapamycin or cyclosporine A was administered simultaneously with LPS. The lowest percentage of DC was noted in an environment of cyclosporine A. Conclusions: We have shown that the environment of immunosuppressive agents: rapamycin and cyclosporine A impairs DC maturation in response to LPS.