title: 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.
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Su-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Hyoung-Soo
authors.initials: HS
authors.lastname: Cho
authors.forename: Seung-Ha
authors.initials: SH
authors.lastname: Yang
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Shin
authors.forename: Jung-Sik
authors.initials: JS
authors.lastname: Kim
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Roh
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D005452:Fluoresceins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013234:Stem Cells / Q000737:chemistry*; D013388:Succinimides / Q000378:metabolism; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000502:physiology*
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D015703:Antigens, CD; D017077:Culture Media, Conditioned; D016207:Cytokines; D005452:Fluoresceins; D019253:Proto-Oncogene Proteins c-bcl-2; D013388:Succinimides