Human MBP-specific T cells regulate IL-6 gene expression in astrocytes through cell-cell contacts and soluble factors

Citation
M. Colombatti et al., Human MBP-specific T cells regulate IL-6 gene expression in astrocytes through cell-cell contacts and soluble factors, GLIA, 35(3), 2001, pp. 224-233
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
GLIA
ISSN journal
0894-1491 → ACNP
Volume
35
Issue
3
Year of publication
2001
Pages
224 - 233
Database
ISI
SICI code
0894-1491(200109)35:3<224:HMTCRI>2.0.ZU;2-S
Abstract
One of the distinctive features of multiple sclerosis (MS) attacks is homin g to the CNS of activated T cells able to orchestrate humoral and cell-base d events, resulting in immune-mediated injury to myelin and oligodendrocyte s. Of the complex interplay occurring between T cells and CNS constituents, we have examined some aspects of T-cell interactions with astrocytes, the major components of the glial cells. Specifically, we focused on the abilit y of T cells to regulate the gene expression of interleukin-6 (IL-6) in ast rocytes, based on previous evidence showing the involvement of this cytokin e in CNS disorders. We found that T-cell adhesion and T-cell soluble factor s induce IL-6 gene expression in U251 astrocytes through distinct signaling pathways, respectively, resulting in the activation of NF-kappaB and IRF-1 transcription factors. In a search for effector molecules at the astrocyte surface, we found that alpha3 beta1 integrins play a role in NF-kappaB act ivation induced by T-cell contact, whereas interferon-gamma (IFN-gamma) rec eptors dominate in IRF-1 induction brought about by T-cell-derived soluble factors. Similar phenomena were observed also in normal fetal astrocyte cul tures. We therefore propose that through astrocyte induction, T cells may i ndirectly regulate the availability of a cytokine which is crucial in modul ating fate and behavior of cell populations involved in the pathogenesis of MS inflammatory lesions. (C) 2001 Wiley-Liss, Inc.