title: Cross-talk between CD4+ T-cells and neural stem/progenitor cells.
abstract: Immune-neural interactions dictate both lesion formation and repair in multiple sclerosis (MS). MS pathogenesis is mediated by the interplay of invading immune cells, neurons, glia, and endogenous stores of neural stem/progenitor cells (NPCs). However, the signals important in this cross-talk are not well defined. We utilized a co-culture method and flow cytometric analysis capable of detecting outcomes for both cell types. Here we describe the effects of NPCs on three different CD4+ subtypes (Th1, Th2, and Th17) and vice versa. Utilizing lpr (Fas receptor-deficient) and gld (Fas ligand-deficient) NPC lines, we further define the role of Fas in this neuroimmune cross-talk. We show that only the Th1 subtype is capable of inducing NPC cell death, and this is independent of Fas activation. Conversely, NPCs specifically kill pro-inflammatory Th1 and Th17 cells in a contact-dependent manner without affecting Th2 survival. Further investigation into these effects revealed that FasL expressed by NPCs mediates Th17 apoptosis. Additionally NPC/T-cell cross-talk modulates FasL expression in both cell types, while Fas receptor levels remains static. These findings illuminate the direct neuropathogenic effects of T-cells, as well as help define the immunomodulatory capacity of NPCs. We have elucidated novel interactions that may be critical in MS pathogenesis.
authors.affiliation: Neuroscience Graduate Program, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Knight
authors.forename: Charles
authors.initials: C
authors.lastname: Hackett
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Breton
authors.forename: Yang
authors.initials: Y
authors.lastname: Mao-Draayer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000502:physiology*; D018417:Th1 Cells / Q000502:physiology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D019014:fas Receptor