The Journal of Experimental Medicine
ELISpot, FluoroSpot and ELISA kits from Mabtech
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online
doi:10.1084/jem.20071878
The Journal of Experimental Medicine, Vol. 205, No. 1, 207-218
The Rockefeller University Press, 0022-1007 $30.00
© Jain et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 3446K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jain, R.
Right arrow Articles by Zaghouani, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jain, R.
Right arrow Articles by Zaghouani, H.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

ARTICLE

 Innocuous IFN{gamma} induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production

Renu Jain1, Danielle M. Tartar1, Randal K. Gregg1, Rohit D. Divekar1, J. Jeremiah Bell1, Hyun-Hee Lee1, Ping Yu1, Jason S. Ellis1, Christine M. Hoeman1, Craig L. Franklin2, and Habib Zaghouani1,3

1 Department of Molecular Microbiology and Immunology, 2 Department of Veterinary Pathobiology, and 3 Department of Child Health, University of Missouri, Columbia, MO 65212

CORRESPONDENCE Habib Zaghouani: zaghouanih{at}health.missouri.edu

The role of Th17 cells in type I diabetes (TID) remains largely unknown. Glutamic acid decarboxylase (GAD) sequence 206–220 (designated GAD2) represents a late-stage epitope, but GAD2-specific T cell receptor transgenic T cells producing interferon {gamma} (IFN{gamma}) protect against passive TID. Because IFN{gamma} is known to inhibit Th17 cells, effective presentation of GAD2 peptide under noninflammatory conditions may protect against TID at advanced disease stages. To test this premise, GAD2 was genetically incorporated into an immunoglobulin (Ig) molecule to magnify tolerance, and the resulting Ig-GAD2 was tested against TID at different stages of the disease. The findings indicated that Ig-GAD2 could not prevent TID at the preinsulitis phase, but delayed TID at the insulitis stage. More importantly, Ig-GAD2 sustained both clearance of pancreatic cell infiltration and β-cell division and restored normoglycemia when given to hyperglycemic mice at the prediabetic stage. This was dependent on the induction of splenic IFN{gamma} that inhibited interleukin (IL)-17 production. In fact, neutralization of IFN{gamma} led to a significant increase in the frequency of Th17 cells, and the treatment became nonprotective. Thus, IFN{gamma} induced by an adjuvant free antigen, contrary to its usual inflammatory function, restores normoglycemia, most likely by localized bystander suppression of pathogenic IL-17–producing cells.

Abbreviations used: GAD, glutamic acid decarboxylase; HEL, hen egg lysozyme; IAA, insulin autoantibody; TID, type I diabetes.

R.K. Gregg's present address is Dept. of Basic Sciences, Philadelphia College of Osteopathic Medicine, Suwanne, GA 30024.

J. J. Bell's present address is Dept. of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104.

P. Yu's present address is National Cancer Institute Metabolism Branch, Bethesda, MD 20892.

H.-H. Lee's present address is Division of Immunology, Karp Laboratories, Children's Hospital, Harvard Medical School, Boston, MA 02115.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS