Expression and biological function of programmed death ligands in human placenta mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) play important roles in tissue regeneration due to their self-renewal, multilineage differentiation and immunosuppression abilities. MSCs can be isolated from various kinds of tissue, such as umbilical cord, cord blood and placenta. Human placenta mesenchymal stem cells (hPMSCs) possess stronger immunosuppressive properties, such as the ability to inhibit T-cell activation and proliferation, than human bone marrow MSCs. We have investigated that the roles of the programmed death ligands 1 and 2 (PDL1 and PDL2) in hPMSC adhesion, migration and immunosuppression were investigated. PDL1 and PDL2 were highly expressed by hPMSCs. Knockdown of PDL1 and/or PDL2 by siRNA increased hPMSC adhesion, but greatly decreasing migration. PDL1 and PDL2 expressed on hPMSCs inhibited T-cell proliferation by arresting the cell cycle. Knockdown of PDL1 and/or PDL2 in hPMSCs, however, had no effect on the expression of CD69, a T-cell early activation marker found on both CD4(+) and CD8(+) T-cell subsets. In summary, the roles of the negative co-stimulators PDL1 and PDL2 is on the adhesion, migration and immunosuppression of hPMSCs. These findings may be useful regarding the potential use of hPMSCs in clinical cell.

Interferon-γ and tumor necrosis factor-α promote the ability of human placenta–derived mesenchymal stromal cells to express programmed death ligand-2 and induce the differentiation of CD4+interleukin-10+ and CD8+interleukin-10+Treg subsets

“…including being positive for CD44, CD29, CD105 and CD166 and negative for the hematopoietic cell surface markers of CD14, CD34 and CD45, consistent with the previous report [16].…”

“…PDL1 and programmed death ligand-2 (PDL2) are the members of B7 family, and the engagement of their receptor, programmed death 1 (PD-1), negatively regulates immune response [15]. In addition, we showed that PDL2 was highly expressed in hPMSCs and promoted hPMSC immunosuppressive ability on activated T cells [16]. Nevertheless, whether PDL2 was also involved in the secretion of IL-10 from the activated T cells regulated by hPMSCs is not clear.…”

“…Human PMSCs were isolated as described in our previous study [16]. Briefly, human term placentas were obtained from unrelated donors who signed the informed consents.…”

“…Cells were identified through morphology under a light microscope and showed positive surface staining for CD44, CD29, CD166 and CD105 but negative surface staining for CD34, CD14 and CD45. The cells were used in the experiments after three passages [16].…”

Granulocyte-like myeloid derived suppressor cells (G-MDSC) are increased in multiple myeloma and are driven by dysfunctional mesenchymal stem cells (MSC)

“…Indeed, MSC can interfere with the recognition of tumor cells by immune system producing and releasing immunoregulatory factors as TGFβ, prostaglandin E2 (PGE2), tumor necrosis factor α (TNFα), indolamine 2, 3-dioxygenase (IDO), hemeoxygenase (HO), NOS2, ARG 1–2 , IL10 [29–32]. MSC express programmed death ligand 1 (PD-L1) that after its engagement with PD-1 expressed on T lymphocytes lead to the inhibition of T cell activation and proliferation with an inefficient immune response [29, 33]. …”