Immunoregulatory Properties of Human Bone Marrow Mesenchymal Stem Cells on T Lymphocyte Proliferation



Karimi MM¹ ; Adib M¹ ; Beni BH² ; Alipour R¹ ; Hassanzadeh A³
Source: Journal of Isfahan Medical School Published:2012

Abstract

Background: Bone marrow mesenchymal stem cells (BM-MSCs) have been shown to be highly immunosuppressive. In some studies, MSCs were found to suppress T cell proliferation and cytokine production. Most researchers reported this effect to be mediated by soluble factors including IL-10, TGF-β1, nitric oxide, indoleamine 2,3-dioxygenase (IDO), and prostaglandin (PG) E2. Others however claim that cell-to-cell contact is necessary. Since the exact mechanism is still uncertain, this study tried to determine the mechanism underlying the immunoregulatory properties of human BMMSCs and their ability to inhibit T-cell proliferation. In addition, role of cell-cell contact and dosedependent immunomodulatory activities of these cell were explored. Methods: In this study, both mitogen- and alloantigen-activated T cells were cultured in the presence of different numbers of BM-MSCs. In some co-cultures, activated T cells were in direct contact to BM-MSC and in other co-cultures, they were separated from BM-MSCs by a permeable membrane. The proliferation of T lymphocytes was assayed with a cell proliferation enzyme-linked immunosorbent assay (ELISA) (Brdu). Findings: Although proliferation index of unstimulated T cells did not significantly differ in the presence or absence of BM-MSCs, the index was inversely related with BM-MSC presence in stimulated cells. Generally, the presence of BM-MSC resulted in a statistically significant decrease in PHA/alloantigen-induced proliferation of T lymphocytes. In addition, proliferation was significantly lower in transwell cultures than in stimulated lymphocytes without BM-MSCs (P < 0.05). Conclusion: The present study showed that BM-MSC suppressed T cells proliferation triggered by allogeneic PBMCs and mitogen (PHA). This effect is dose dependent and BM-MSCs do not necessarily require the cell-to-cell contact (direct contact) of MSC and lymphocytes. However, the suppression is reduced to some extent by the physical separation of MSCs and immune cells (indirect contact).