THE ROLE OF INTERCELLULAR CONTACTS IN THE INDUCTION OF IDO EXPRESSION IN THE ADIPOSE DERIVED MMSCs
The investigation of interaction of human multipotetnt mesenchymal stromal cells (MMSCs) and stimulated immune cells in vitro is an important step in understanding of molecular mechanisms of inflammation and tissue regeneration. In this study we have demonstrated that MMSCs derived from human adipose exhibit the immunosuppressive effect on proliferation of the peripheral blood mononuclear cells (PBMC) stimulated by phytohemagglutinin in both contact and contactless co-culture. Co-culture enhanced the ability of stimulated CD4+ T-lymphocytes to form a stable adherens junction with MMSCs. Expression of membrane intercellular adhesion molecule (ICAM-1) in MMSCs was elevated upon co-cultivation with stimulated PBMCs. The pro-inflammatory microenvironment produced by stimulated PBMCs also induced the expression of costimulatory molecules CD80/CD86 in MMSCs. ICAM-1 and CD80/CD86 molecules expressed on the MMSCs surface participate in establishment of cell-cell contacts with CD4+ T-cells through the interaction with their counter receptors LFA-1 and CTLA4/CD28. Intercellular interaction between stimulated CD4+ T-lymphocytes and MMSCs is responsible for enhanced production of IFN-g and the induction of expression and activation of indoleamin-2,3-dioxygenase (IDO) in MMSC. Taking together, our findings shed a light on the mechanism underlying the immunosuppressive effects of MMSC depending on intercellular interactions with stimulated CD4+-lymphocytes.