PMID: 8610991Feb 13, 1996Paper

Active suppression of diabetes after oral administration of insulin is determined by antigen dosage

Annals of the New York Academy of Sciences
I BergerotC Thivolet

Abstract

We have previously demonstrated that feeding six-week-old female mice with 20 units of human insulin every 2 - 3 days for 15 or 30 days induced an active mechanism of suppression through the generation of regulatory T cells that reduced the number of successful diabetic transfers in irradiated NOD recipients. In the present study, we analyzed the effects of antigen dosage and the critical period of cell injection to obtain protection. The effects of the dose of insulin feeding were therefore compared during cotransfer experiments of 5 x 10(6) T cells from diabetic mice and 5 x 10(6) T cells from the spleen of mice receiving 10 units, 20 units, or 40 units of insulin or saline every 2 - 3 days for 15 days. Only T lymphocytes from mice fed with 20 units conferred active cellular protection during adoptive transfer with a significant delay in diabetes onset (p = 0.002). No significant difference was noticed during histological analysis of pancreatic glands, indicating tha insulitis was not prevented. However, mice receiving T lymphocytes from the 20 units of insulin-fed animals had a milder form of inflammation, with a significantly lower percentage of severely infiltrated islets. Injecting regulatory T cells 7 days and 14 days af...Continue Reading

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Citations

May 1, 2008·Current Diabetes Reports·Peter AchenbachUNKNOWN Pre-POINT Study Group
Jun 2, 2011·Nature Reviews. Drug Discovery·Frank Waldron-Lynch, Kevan C Herold
Nov 9, 2005·The Journal of Experimental Medicine·Matthias G von Herrath, Gerald T Nepom
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·K J BeckerJ M Hallenbeck
Jan 28, 2015·Nature Reviews. Endocrinology·James C Reed, Kevan C Herold
Apr 1, 2004·Endocrinology and Metabolism Clinics of North America·Urs ChristenMatthias G von Herrath
Feb 19, 2000·Gene Therapy·C M Seroogy, C G Fathman
Jan 8, 2004·Annals of Medicine·Arno HänninenChristian Kurts
Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S H ImS Fuchs

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