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

• Published in: Journal of neuroscience research 2009-08, Vol.87 (10), p.2264-2272
• Main Authors: Kim, Su-Young, Cho, Hyoung-Soo, Yang, Seung-Ha, Shin, Jin-Young, Kim, Jung-Sik, Lee, Soon-Tae, Chu, Kon, Roh, Jae-Kyu, Kim, Seung U., Park, Chung-Gyu
• Format: Article
• Language: English
• Subjects: Antigens, CD - metabolism; apoptosis; Apoptosis - drug effects; Cell Cycle - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Culture Media, Conditioned - pharmacology; Cytokines - metabolism; Flow Cytometry - methods; Fluoresceins - metabolism; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; HB1.F3; human neural stem cells (hNSCs); Humans; Lymphocyte Activation - drug effects; Lymphocyte Activation - physiology; Neurons - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; soluble mediator; Stem Cells - chemistry; Succinimides - metabolism; T-cell suppression; T-Lymphocytes - classification; T-Lymphocytes - drug effects; T-Lymphocytes - physiology
• ISSN: 0360-4012; 1097-4547; 1097-4547
• DOI: 10.1002/jnr.22050

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‐α, and interferon‐γ 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. © 2009 Wiley‐Liss, Inc.