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.
Keywords
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Article info
Publication history
Published online: April 15, 2011
Accepted:
March 15,
2011
Received in revised form:
January 25,
2011
Received:
November 3,
2010
Identification
Copyright
Published by Elsevier Inc.
