Figure 1.

Immunomodulatory properties of mesenchymal stem cells (MSCs). (A) MSCs can target several subsets of lymphocytes, including CD4⁺ helper T-lymphocytes (Ths), CD8⁺ cytotoxic T-lymphocytes (CTLs), gammadelta T-cells, natural killer (NK) cells, B-lymphocytes, and regulatory T-lymphocytes (Tregs). These effects may be mediated by several soluble factors secreted by MSCs, including, for example, prostaglandin E₂ (PGE₂), transforming growth factor-β1 (TGF β1), nitric oxide (NO), indoleamine 2,3-dioxygenase (IDO), or hepatocyte growth factor (HGF). (B) Infused MSCs can induce T-cell apoptosis through FAS/FASL-mediated multiple paracrine interactions and cell-cell contacts, as well as promoting the generation of Tregs, which ultimately leads to immune tolerance. This process consists of the following stages: (1) MSCs use FAS to control monocyte chemotactic protein 1 (MCP-1) secretion, and MCP-1 recruits activated T-cells; (2) MSCs use FASL to induce activated T-cell apoptosis; (3) apoptotic T-cells subsequently trigger macrophages to produce high levels of TGFβ; and (4) the high level of TGFβ up-regulates Tregs to induce immune tolerance.