Mucosal antigen primes diabetogenic cytotoxic T-Lymphocytes regardless of dose or delivery route

Citation
A. Hanninen et al., Mucosal antigen primes diabetogenic cytotoxic T-Lymphocytes regardless of dose or delivery route, DIABETES, 50(4), 2001, pp. 771-775
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
DIABETES
ISSN journal
0012-1797 → ACNP
Volume
50
Issue
4
Year of publication
2001
Pages
771 - 775
Database
ISI
SICI code
0012-1797(200104)50:4<771:MAPDCT>2.0.ZU;2-U
Abstract
Administration of antigens via mucosal routes, such as orally or intranasal ly, can induce specific immunological tolerance and has been used as a rati onal basis for the treatment of autoimmune diseases, including type 1 diabe tes. Recently, however, orally delivered antigens mere shown to induce CD8 cytotoxic T-lymphocytes (CTLs) capable of causing autoimmune diabetes. In t his report, we have examined several mucosal routes for their ability to in duce CTLs and autoimmune diabetes, with the aim of identifying approaches t hat would maximize tolerance and minimize CTL generation, In normal C57BL/6 mice, ovalbumin (OVA) delivered by either the oral or nasal routes or by a erosol inhalation was able to prime CTL immunity in both high- and low-dose regimens. To address the relevance of these CTLs to autoimmune disease, OV A was given to mice that transgenically expressed this antigen in their pan creatic beta -cells. Irrespective of antigen dose or the route of delivery, mucosal OVA triggered diabetes, particularly after intranasal administrati on. These findings suggest that CTL immunity is likely to be a consequence of mucosal antigen delivery, regardless of the regimen, and should be consi dered in the clinical application of mucosal tolerance to autoimmune diseas e prevention.