The Role of Intercellular Contacts in Induction of Indolamine-2,3-Dioxygenase Synthesis in MMSC from Adipose Tissue

Abstract

Modeling the interaction of multipotent mesenchymal stromal cells (MMSC) and activated immune cells in vitro is an important step in the study of molecular mechanisms of inflammation and tissue regeneration. Under our experimental conditions, we demonstrated that, upon cocultivation under contact and contact-free conditions, MMSC isolated from human adipose tissue suppressed proliferation of peripheral blood mononuclear cells (PBMC) activated by phytohemagglutinin (PHA). It was found that activation leads to an increased ability of CD4⁺ T-lymphocytes to form adhesive contacts with MMSC. In MMSC, cocultivation with activated PBMC increased the synthesis and exposure on the surface of the ICAM-1 adhesion molecule and induced the synthesis of CD80, CD86, and HLA-DR molecules involved in the formation of intercellular contacts with CD4⁺ T-lymphocytes by interaction with their counterreceptors LFA1 and CTLA4/CD28. It was shown that the appearance of intercellular contacts leads to an increase in the production of interferon-gamma (IFN-γ) by CD4⁺ T-lymphocytes and induction of the synthesis of indolamine-2,3-dioxygenase (IDO) in MMSCs. The obtained data allowed clarifying the mechanism of MMSC-mediated immunosuppression, which involves contact interactions with activated CD4⁺ T-lymphocytes.