| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Pathology and Immunology, Monash University Medical School, Prahran, Victoria, Australia
Mechanisms leading to breakdown of immunological tolerance and initiation of autoimmunity are poorly understood. Experimental autoimmune gastritis is a paradigm of organ-specific autoimmunity arising from a pathogenic autoimmune response to gastric H/K ATPase. The gastritis is accompanied by autoantibodies to the gastric H/K ATPase. The best characterized model of experimental autoimmune gastritis requires neonatal thymectomy. This procedure disrupts the immune repertoire, limiting its usefulness in understanding how autoimmunity arises in animals with intact immune systems. Here we tested whether local production of GM-CSF, a pro-inflammatory cytokine, is sufficient to break tolerance and initiate autoimmunity. We generated transgenic mice expressing GM-CSF in the stomach. These transgenic mice spontaneously developed gastritis with an incidence of about 80% after six backcrosses to gastritis-susceptible BALBc/CrSlc mice. The gastritis is accompanied by mucosal hypertrophy, enlargement of draining lymph nodes and autoantibodies to gastric H/K ATPase. An infiltrate of dendritic cells and macrophages preceded CD4 T cells into the gastric mucosa. T cells from draining lymph nodes specifically proliferated to the gastric H/K ATPase. CD4 but not CD8 T cells transferred 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 tolerance and initiate autoimmunity mediated by CD4 T cells. This new mouse model should be useful for studies of organ-specific autoimmunity.
This article has been cited by other articles:
|
|
 |
|
  T. Enzler, S. Gillessen, M. Dougan, J. P. Allison, D. Neuberg, D. A. Oble, M. Mihm, and G. Dranoff Functional deficiencies of granulocyte-macrophage colony stimulating factor and interleukin-3 contribute to insulitis and destruction of {beta} cells Blood, August 1, 2007; 110(3): 954 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Esnault, Z.-J. Shen, E. Whitesel, and J. S. Malter The Peptidyl-Prolyl Isomerase Pin1 Regulates Granulocyte-Macrophage Colony-Stimulating Factor mRNA Stability in T Lymphocytes J. Immunol., November 15, 2006; 177(10): 6999 - 7006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. C. Hornell, G. W. Beresford, A. Bushey, J. M. Boss, and E. D. Mellins Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor J. Immunol., September 1, 2003; 171(5): 2374 - 2383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Murphy, M. Biondo, B.-H. Toh, and F. Alderuccio Tolerance established in autoimmune disease by mating or bone marrow transplantation that target autoantigen to thymus Int. Immunol., January 1, 2003; 15(2): 269 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. McQualter, R. Darwiche, C. Ewing, M. Onuki, T. W. Kay, J. A. Hamilton, H. H. Reid, and C. C.A. Bernard Granulocyte Macrophage Colony-stimulating Factor: A New Putative Therapeutic Target in Multiple Sclerosis J. Exp. Med., September 24, 2001; 194(7): 873 - 882. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
