Local transgenic expression of granulocyte macrophage-colony stimulating factor initiates autoimmunity

Citation
M. Biondo et al., Local transgenic expression of granulocyte macrophage-colony stimulating factor initiates autoimmunity, J IMMUNOL, 166(3), 2001, pp. 2090-2099
Citations number
62
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
0022-1767 → ACNP
Volume
166
Issue
3
Year of publication
2001
Pages
2090 - 2099
Database
ISI
SICI code
0022-1767(20010201)166:3<2090:LTEOGM>2.0.ZU;2-T
Abstract
Mechanisms leading to breakdown of immunological tolerance and initiation o f autoimmunity are poorly understood. Experimental autoimmune gastritis is a paradigm of organ-specific autoimmunity arising from a pathogenic autoimm une response to gastric WK ATPase, The gastritis is accompanied by autoanti bodies to the gastric WK ATPase, The best characterized model of experiment al autoimmune gastritis requires neonatal thymectomy, This procedure disrup ts the immune repertoire, limiting its usefulness in understanding how auto immunity arises in animals with intact immune systems, Here we tested wheth er local production of GM-CSF, a pro-inflammatory cytokine, is sufficient t o break tolerance and initiate autoimmunity. We generated transgenic mice e xpressing GM-CSF in the stomach, These transgenic mice spontaneously develo ped gastritis with an incidence of about 80% after six backcrosses to gastr itis-susceptible BALBc/CrSlc mire. The gastritis is accompanied by mucosal hypertrophy, enlargement of draining lymph nodes and autoantibodies to gast ric WK ATPase, An infiltrate of dendritic cells and macrophages preceded CD 4 T cells into the gastric mucosa, T cells from draining lymph nodes specif ically proliferated to the gastric WK ATPase, CD4 but not CD8 T cells trans ferred gastritis to nude mouse recipients. CD4(+) CD25(+) T cells from the spleen retained anergic suppressive properties that were reversed by IL-2. We conclude that local expression of GM-CSF is sufficient to break toleranc e and initiate autoimmunity mediated by CD4 T cells. This new mouse model s hould be useful for studies of organ-specific autoimmunity.