The Immunomodulatory Properties of Mesenchymal Stem Cells Play a Critical Role in Inducing Immune Tolerance after Liver Transplantation

Figure 1

The mechanism of immune rejection after liver transplantation. (a) Immune rejection mediated by cellular immunity. Antigen-presenting cells (APCs) recognize and uptake the foreign antigens from donor-derived cells and present them to T cells, in which CD4+ T cells are activated and differentiate into various effector T cells, such as T helper 1 (Th1), Th2, and cytotoxic T lymphocytes (CTLs). Th1 cells can induce CD8+ T cells to differentiate into cytotoxic T lymphocytes (CTLs) via secreting IL2, and CTLs can secrete perforin to directly lyse hepatocytes or induce target cell apoptosis through the Fas-FasL pathway. On the other hand, Th1 cells can secrete interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and lymphotoxin to corrupt liver grafts via delayed-type hypersensitivity (DTH), in the process of which macrophages may be a primary participant and play a critical role. (b) Immune rejection mediated by humoral immunity. B cells can directly recognize donor antigens without the antigen presentation of APC, which will be subsequently activated and differentiated into plasmocytes with the help of Th2 cells, and secrete antibodies to destroy donor cells. TCR: T cell receptor; BCR: B cell receptor; HLA: human leukocyte antigen.