International Immunology, Vol. 13, No. 10, 1321-1333,
October 2001
© 2001 Japanese Society for Immunology
Relative resistance to nasally induced tolerance in non-obese diabetic mice but not other I-Ag7-expressing mouse strains
La Jolla Institute for Allergy and Immunology, Division of Immune Regulation, and
1 Division of Cellular Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
2 Department of Microbiology and Molecular Genetics, University of California, Los Angeles,CA 90095-1489, USA
Correspondence to: Correspondence to: A. Quinn
I-Ag7 is a unique class II MHC molecule that is clearly associated with autoimmune diabetes in non-obese diabetic (NOD) mice. To determine if I-Ag7 is defective in its ability to deliver tolerogenic signals in vivo, H-2g7 mice were nasally pretreated with antigen, prior to immunization, to induce antigen-specific regulation. Nasally pretreated NOR (H-2g7) and (NON).NOD (H-2g7) congenic mice showed responses similar to those of NON (H-2nb1), BALB/c (H-2d) and B10.PL (H-2u) mice—a reduced recall response and a deviated Th cytokine profile. However, we found that NOD (H-2g7) mice are comparatively resistant to immunological tolerance induced by nasal pretreatment, such that at the usually effective dose no significant reduction was seen in the proliferative recall responses to nominal antigen after immunization. (NOD x BALB/c)F1 (H-2g7/d) and (NOD x NOR)F1 (H-2g7) mice were similarly resistant to nasal-induced tolerance, although significantly higher nasal doses of antigen were able to overcome the resistance in NOD and F1 mice. Interestingly, activated NOD T cells were resistant to cell death induced by re-stimulation with plate-bound anti-CD3. These results demonstrate that activated T cells in NOD mice are defective in their ability to respond to regulatory signals delivered in vivo or in vitro. Furthermore, NOD T cells have an increased resistance to tolerance induced by I-Ag7-dependent (antigen) or I-Ag7-independent (anti-CD3) mechanisms. Thus, while I-Ag7 may contribute to insulin-dependent diabetes mellitus by selecting a particular repertoire of self-reactive T cell clones, additional defects in the peripheral T cells themselves are required to allow the expansion of diabetogenic clones and the development of autoimmune disease.
Keywords: apoptosis, immune deviation, hen egg lysozyme, mucosal, T cells
3 Present address: Department of Immunology, Holland Laboratory, American Red Cross, Rockville, MD 208552, USA
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Ejrnaes, N. Videbaek, U. Christen, A. Cooke, B. K. Michelsen, and M. von Herrath Different Diabetogenic Potential of Autoaggressive CD8+ Clones Associated with IFN-{gamma}-Inducible Protein 10 (CXC Chemokine Ligand 10) Production but Not Cytokine Expression, Cytolytic Activity, or Homing Characteristics J. Immunol., March 1, 2005; 174(5): 2746 - 2755. [Abstract] [Full Text] [PDF]
|
|