Human Mesenchymal Stem Cells from Adipose Tissue and Amnion Influence T-Cells Depending on Stimulation Method and Presence of Other Immune Cells

Abstract

Mesenchymal stem cells (MSCs) are multipotent progenitor cells exerting immunomodulatory effects on cells of the innate and adaptive immune system. It has been shown that an inflammatory milieu is required for the activation of MSC-mediated immunomodulation, and interferon-γ (IFN-γ) plays an important role in this process. We determined the influence of IFN-γ on human adipose-derived stem cells (ASCs) and human amniotic mesenchymal stromal cells (hAMSCs). We further evaluated the effect of MSCs on stimulated T-cells and peripheral blood mononuclear cells (PBMCs) in a cell-contact independent setting. On IFN-γ treatment, ASCs and hAMSCs possessed significantly higher antiproliferative properties and showed surface characteristics of nonprofessional antigen presenting cells (HLA-DR(+)CD40(med+)CD54(high)) with a possible regulatory phenotype (PD-L1(+)PD-L2(+)). The effect of ASCs and hAMSCs on cytokine secretion and T-cell activation was dependent on stimulation method and cellular context. Although ASCs and hAMSCs highly inhibited cytokine secretion of stimulated PBMCs, this was not observed in the case of purified T-cells. The presence of ASCs even favored the secretion of pro-inflammatory cytokines including IFN-γ by T-cells, although T-cell proliferation was efficiently inhibited. Further, ASCs enhanced the number of CD69(+) T-cells independent of the stimuli and cellular context. Interestingly, ASCs significantly suppressed CD25 expression on phytohemagglutinin stimulated PBMCs but had no effect on αCD3/αCD28 stimulated cells. Depending on the stimulation method and cellular context, immune cells create a specific cytokine milieu in vitro, thus differently influencing MSCs and, in turn, affecting their action on immune cells.

Human Mesenchymal Stromal Cells from Adult and Neonatal Sources: A Comparative In Vitro Analysis of Their Immunosuppressive Properties Against T Cells

“…+ T cells) and the presence of cell contact in cocultures with MSCs in BM-MSCs-mediated immunosuppression [9,14]. Thus, we decided to analyze the direct effect of MSCs on a CD3…”

“…However, few studies have been performed with enriched populations of CD3 + T cells [10,13,14]. This is important because CD4 + and CD8 + T cells are the major effector cells in immunological diseases such as graft-versus-host disease (GVHD) [15], and thus it is important to determine the immunosuppression properties of MSCs on these populations and determine their potential for cell therapies.…”

Human mesenchymal stromal cells modulate T‐cell responses through TNF‐α‐mediated activation of NF‐κB

“…regard, the focus of this study was to investigate the functional role of NF-κB in the "priming" of MSCs in an inflammatory environment; in particular, the importance of the TNF-α/NF-κB axis. MSC-induced immunosuppression is a complex phenomenon that appears to function differently depending on the T-cellderived cytokines and membrane molecules that are present, leading to a variety of responses from MSCs [9,28,29]. TNF-α is one such critical cytokine, which is known to activate the NF-κB cascade [25].…”

Adipose-derived stromal/stem cells

“…These include: indoleamine 2,3 dioxygenase (IDO), a rate limiting enzyme in tryptophan metabolism that is associated with suppression of T lymphocyte expansion; prostaglandin E2 (PGE2) and; transforming growth factor β. 38,[40][41][42][43][44] When co-cultured with peripheral blood monocytes, ASCs support the expansion of CD25 positive T-regulatory cells, which in turn are responsible for suppression of immune responses. 41 This interaction can be further enhanced under blood lymphoid cell, a positive MLR was observed (Fig.…”