%0 Journal Article %1 wang2009neural %A Wang, L %A Shi, J %A van Ginkel, F W %A Lan, L %A Niemeyer, G %A Martin, D R %A Snyder, E Y %A Cox, N R %D 2009 %J Exp Neurol %K npc phd stemcell transplantation %N 1 %P 177--183 %R 10.1016/j.expneurol.2008.11.017 %T Neural stem/progenitor cells modulate immune responses by suppressing T lymphocytes with nitric oxide and prostaglandin E2 %U http://www.ncbi.nlm.nih.gov/pubmed/19109951 %V 216 %X We and others have reported that neural stem/progenitor cells (NSCs) may exert direct anti-inflammatory activity. This action has been attributed, in part, to T-cell suppression. However, how T-cells become suppressed by NSCs remains unresolved. In this study, we explored one of these mechanisms and challenged some previously advanced hypotheses regarding underlying NSC-mediated T-cell suppression. We employed an easily observable and manipulatable system in which activated and non-activated T-cells were co-cultured with a stable well-characterized clone of lacZ-expressing murine NSCs. As in previous reports, NSCs were found to inhibit T-cell proliferation. However, this inhibition by NSCs was not due to suppression of T cell activation or induction of apoptosis of T cells during the early activation stage. High levels of nitric oxide (NO) and prostaglandin E2 (PGE2) were induced in the T cells when co-cultured with NSCs. In addition, inducible NOS (iNOS) and microsomal type 1 PGES (mPGES-1) were readily detected in NSCs in co-culture with T-cells, but not at all in NSCs cultured alone or in activated T cells cultured with or without NSCs. This finding suggested that activated T cells induced NO and PGE2 production in the NSCs. Furthermore, T-cell proliferation inhibited by co-culture with the NSCs was significantly restored by inhibitors of NO and PGE2 production. Therefore, NSCs appear to suppress T-cells, at least in part, by NO and PGE2 production which, in turn, would account for the well-documented reduction of central nervous system immunopathology by transplanted NSCs.

@article{wang2009neural, abstract = {We and others have reported that neural stem/progenitor cells (NSCs) may exert direct anti-inflammatory activity. This action has been attributed, in part, to T-cell suppression. However, how T-cells become suppressed by NSCs remains unresolved. In this study, we explored one of these mechanisms and challenged some previously advanced hypotheses regarding underlying NSC-mediated T-cell suppression. We employed an easily observable and manipulatable system in which activated and non-activated T-cells were co-cultured with a stable well-characterized clone of lacZ-expressing murine NSCs. As in previous reports, NSCs were found to inhibit T-cell proliferation. However, this inhibition by NSCs was not due to suppression of T cell activation or induction of apoptosis of T cells during the early activation stage. High levels of nitric oxide (NO) and prostaglandin E2 (PGE2) were induced in the T cells when co-cultured with NSCs. In addition, inducible NOS (iNOS) and microsomal type 1 PGES (mPGES-1) were readily detected in NSCs in co-culture with T-cells, but not at all in NSCs cultured alone or in activated T cells cultured with or without NSCs. This finding suggested that activated T cells induced NO and PGE2 production in the NSCs. Furthermore, T-cell proliferation inhibited by co-culture with the NSCs was significantly restored by inhibitors of NO and PGE2 production. Therefore, NSCs appear to suppress T-cells, at least in part, by NO and PGE2 production which, in turn, would account for the well-documented reduction of central nervous system immunopathology by transplanted NSCs.}, added-at = {2013-04-04T14:21:59.000+0200}, author = {Wang, L and Shi, J and van Ginkel, F W and Lan, L and Niemeyer, G and Martin, D R and Snyder, E Y and Cox, N R}, biburl = {https://www.bibsonomy.org/bibtex/268c615ce83c7382d1912916d48a9c49a/bkoch}, description = {Neural stem/progenitor cells modulate immune resp... [Exp Neurol. 2009] - PubMed - NCBI}, doi = {10.1016/j.expneurol.2008.11.017}, interhash = {6df709beb05c207ae7eba503c33b81e4}, intrahash = {68c615ce83c7382d1912916d48a9c49a}, journal = {Exp Neurol}, keywords = {npc phd stemcell transplantation}, month = mar, number = 1, pages = {177--183}, pmid = {19109951}, timestamp = {2013-04-04T14:21:59.000+0200}, title = {Neural stem/progenitor cells modulate immune responses by suppressing T lymphocytes with nitric oxide and prostaglandin E2}, url = {http://www.ncbi.nlm.nih.gov/pubmed/19109951}, volume = 216, year = 2009 }