Neural Stem/Progenitor Cells Induce Conversion of Encephalitogenic T Cells into CD4+-CD25+- FOXP3+ Regulatory T cells

Abstract

An immune role of neural stem/progenitor cells (NSPCs) has been proposed in many recent studies; however much still remains to be elucidated. In the current investigation, we report that NSPCs possess the ability to convert encephalitogenic T cells into CD4+-CD25+-FOXP3+ regulatory T cells (Treg). Encephalitogenic and nonencephalitogenic T cells isolated from sham and Japanese encephalitis virus (JEV) infected animals were co-cultured with mouse NSPCs. Post co-culture, significant increase in the number of Tregs was observed from encephalitogenic T cells co-cultured with NSPCs. This increased conversion was found to be dependent on direct contact between T cells and NSPCs. Neutralization of TGF-β and IFN-γ in NSPC cultures abrogated this increased conversion of encephalitogenic T cells into Tregs. Flow cytometric, quantitative RT-PCR, and immunoblot analysis of both T cells and NSPCs revealed surface and intracellular changes post co-culture. Co-stimulatory molecules (B7) and ICAM-1 were increased on NSPCs post co-culture; levels of TGFβ, IFNγ, and TGFβR1 were also increased in NSPCs. This study provides a basic insight into the interaction between CNS-infiltrating encephalitogenic T cells and NSPCs during viral encephalitis. Conversion of encephalitogenic T cells into CD4+-CD25+-FOXP3+ Tregs through interaction with NSPCs indicates an attempt in regulation of excessive inflammation in the CNS.