title: 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 (T(reg)). 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 T(regs) 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 T(regs). 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(+) T(regs) through interaction with NSPCs indicates an attempt in regulation of excessive inflammation in the CNS.
authors.affiliation: National Brain Research Centre , Manesar, Haryana, India .
authors.forename: Arshed
authors.initials: A
authors.lastname: Nazmi
authors.forename: Iqbal
authors.initials: I
authors.lastname: Mohamed Arif
authors.forename: Kallol
authors.initials: K
authors.lastname: Dutta
authors.forename: Kiran
authors.initials: K
authors.lastname: Kundu
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004664:Encephalitis Virus, Japanese / Q000276:immunology*; D004671:Encephalitis, Arbovirus / Q000276:immunology*; D018177:Flavivirus Infections / Q000276:immunology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D015151:Immunoblotting; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D058953:Neural Stem Cells / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit