Oral administration of human insulin to NOD mice generates CD4+ T cells that suppress adoptive transfer of diabetes

J Autoimmun. 1994 Oct;7(5):655-63. doi: 10.1006/jaut.1994.1050.


Oral administration of porcine insulin has been shown to be effective in preventing the spontaneous occurrence of diabetes in the Non-Obese Diabetic (NOD) mouse model. In the present study, we demonstrate that feeding 6-week-old female mice with 20 units of human insulin every 2-3 days for 30 days induces an active mechanism of suppression through the generation of regulatory T cells. Adult irradiated NOD males i.v. injected with 5 x 10(6) T cells from the spleens of diabetic female donors and the same number of T cells from the spleens of insulin-fed animals had less successful diabetes transfer than controls (4/15 vs. 8/16, P < 0.001). Protection from clinical diabetes was associated with a reduction in severe insulitis (16.4 +/- 3.6% vs. 52.3 +/- 12.8%, P = 0.023). However, more than 85% of the islets were inflamed. Feeding animals for 15 days reduced the magnitude of this protection since the number of successful transfers after 1 month was comparable (12/17 vs. 14/17) despite a significant delay in diabetes onset (P < 0.001). No difference in the contribution of T cell subsets was noted by cytofluorometry in the spleens of treated animals. When T cell subsets from insulin-fed animals were co-injected with diabetogenic T cells, only purified CD4+ T cells were able to transfer protection since only 3/12 mice became diabetic after 36 days in comparison to 3/6 in the group co-injected with CD4+ T cells from PBS-fed animals, or 5/6 in the group injected with CD8+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Animals
  • Autoimmunity
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Female
  • Humans
  • Inflammation
  • Insulin / administration & dosage
  • Insulin / immunology
  • Insulin / therapeutic use*
  • Islets of Langerhans / pathology
  • Isoantigens / administration & dosage
  • Isoantigens / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Species Specificity
  • Spleen
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*


  • Insulin
  • Isoantigens