Soluble mediators from human neural stem cells play a critical role in suppression of T‐cell activation and proliferation

Abstract

Human neural stem cells (hNSCs) can control inflammation in the central nervous system, although the underlying mechanisms are not understood fully. We investigated the immunomodulatory effect of hNSCs on human T cells and the underlying mechanisms. Culture supernatant from an immortalized hNSC cell line, HB1.F3, which has a therapeutic effect on acute stroke and intracerebral hemorrhage, suppressed the proliferation of allogeneically or mitogenically stimulated human peripheral T cells, including the CD3(+)CD103(+) subpopulation. CFSE labeling and flow cytometry showed that the suppression of proliferation was caused by cell cycle arrest and induction of apoptosis. The lack of significant change in caspase-8 levels and the significant reduction in Bcl-2 expression in the affected T cells suggest that the intrinsic pathway plays a major role in soluble-factor-mediated T-cell apoptosis. The addition of culture supernatant from hNSCs to activated T cells reduced the expression of the activation markers CD69 and CD25 at 24 hr after activation, but at 48 hr only CD69 was down-regulated. A cytometry bead assay showed that the secretion of interleukin (IL)-2 decreased significantly, whereas that of IL-4, IL-10, tumor necrosis factor-alpha, and interferon-gamma increased. These results show that hNSCs can negatively affect human peripheral T cells by suppressing their activation and proliferation through soluble mediators, suggesting that hNSCs have a bystander immunomodulatory effect on T cells.

Cancer-Initiating Cells from Colorectal Cancer Patients Escape from T Cell–Mediated Immunosurveillance In Vitro through Membrane-Bound IL-4

“…In fact, proliferation of T cells was inhibited by coculture with autologous or allogeneic CICs, but not with FBS tumor cells. CIC-associated factors, such as TGF-b, IL-10, IL-13, galectin, and PDGE2, which can play a negative regulatory role in the induction of tumor reactive T cells, have been described (12)(13)(14) and, notably, shown to be shared with normal stem cells as well (30). The complexity of this issue is demonstrated by the evidence that none of the molecules described above have been found to be specifically expressed or upregulated in CICs that we have isolated in vitro (data not shown), in line with the results that have been previously published by our group for GBM (10).…”

Culture supernatant of adipose stem cells can ameliorate allergic airway inflammation via recruitment of CD4+CD25+Foxp3 T cells

“…Culture supernatant of human neural stem cells (HB1.F3) has a therapeutic effect on acute stroke and intracerebral hemorrhage, and suppresses the proliferation of human peripheral T cells, including the CD3 + CD103+ subpopulation [8]. After treating T cells with culture supernatant from human neural stem cells, the secretion of IL-2 was significantly decreased, whereas that of IL-4, IL-10, TNF-α, and IFN-γ was increased.…”

“…Recently, it has been reported that culture supernatant of MSCs could suppress T cell proliferation in an in vitro model [8, 9], and that feline mesenchymal stem cell supernatant could inhibit reactive oxygen species production by feline neutrophils [10]. Cruz et al, suggested that human bone marrow-derived cells extracellular vesicles also ameliorate Aspergillus hyphal extract-induced allergic airway inflammation in immunocompetent mice [11].…”

Menstrual blood transplantation for ischemic stroke: Therapeutic mechanisms and practical issues

“…Neural stem cells, for example, decrease the expression of TNF-α and, in consequence, reduce neutrophil infiltration into the CNS of rat models of hemorrhagic stroke [56]. Later in the course of inflammation, stem cells also suppress reactive lymphocytes while enhancing the activity and proliferation of their beneficial, regulatory subsets [57]. Moreover, trophic factors secreted by the stem cells stimulate angiogenesis and repair [58].…”