Mechanism underlying counterregulation of autoimmune diabetes by IL-4

Regula Mueller, Linda M. Bradley, Troy Krahl, Nora E Sarvetnick

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Diabetes in nonobese diabetic (NOD) mice is an autoimmune disease characterized by the destruction of the β cells in the pancreas. We have previously reported that transgenic expression of interleukin-4 (IL-4) counterregulates the disease process, completely protecting NOD mice from insulitis and diabetes. Here we demonstrate the presence of autoreactivity but lack of pathogenicity of the IL-4-regulated lymphocytes. The importance of T cell diversity for the protective effect of IL-4 is demonstrated through breeding with transgenic BDC2.5 mice, which have an almost exclusively monoclonal T cell repertoire. Limitation of T cell diversity abrogated the protection by IL-4. We suggest that 'immune deviation' in NOD-IL-4 mice is mediated by the pancreatic tissue itself, which causes activation of distinct, nonpathogenic T cell specificities.

Original languageEnglish (US)
Pages (from-to)411-418
Number of pages8
JournalImmunity
Volume7
Issue number3
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Fingerprint

Type 1 Diabetes Mellitus
Interleukin-4
Inbred NOD Mouse
T-Lymphocytes
T-Cell Antigen Receptor Specificity
Transgenic Mice
Autoimmune Diseases
Breeding
Virulence
Pancreas
Lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Mechanism underlying counterregulation of autoimmune diabetes by IL-4. / Mueller, Regula; Bradley, Linda M.; Krahl, Troy; Sarvetnick, Nora E.

In: Immunity, Vol. 7, No. 3, 01.01.1997, p. 411-418.

Research output: Contribution to journalArticle

Mueller, Regula ; Bradley, Linda M. ; Krahl, Troy ; Sarvetnick, Nora E. / Mechanism underlying counterregulation of autoimmune diabetes by IL-4. In: Immunity. 1997 ; Vol. 7, No. 3. pp. 411-418.
@article{4589ce6c7be04e0c9b7cd000327d7183,
title = "Mechanism underlying counterregulation of autoimmune diabetes by IL-4",
abstract = "Diabetes in nonobese diabetic (NOD) mice is an autoimmune disease characterized by the destruction of the β cells in the pancreas. We have previously reported that transgenic expression of interleukin-4 (IL-4) counterregulates the disease process, completely protecting NOD mice from insulitis and diabetes. Here we demonstrate the presence of autoreactivity but lack of pathogenicity of the IL-4-regulated lymphocytes. The importance of T cell diversity for the protective effect of IL-4 is demonstrated through breeding with transgenic BDC2.5 mice, which have an almost exclusively monoclonal T cell repertoire. Limitation of T cell diversity abrogated the protection by IL-4. We suggest that 'immune deviation' in NOD-IL-4 mice is mediated by the pancreatic tissue itself, which causes activation of distinct, nonpathogenic T cell specificities.",
author = "Regula Mueller and Bradley, {Linda M.} and Troy Krahl and Sarvetnick, {Nora E}",
year = "1997",
month = "1",
day = "1",
doi = "10.1016/S1074-7613(00)80362-3",
language = "English (US)",
volume = "7",
pages = "411--418",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Mechanism underlying counterregulation of autoimmune diabetes by IL-4

AU - Mueller, Regula

AU - Bradley, Linda M.

AU - Krahl, Troy

AU - Sarvetnick, Nora E

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Diabetes in nonobese diabetic (NOD) mice is an autoimmune disease characterized by the destruction of the β cells in the pancreas. We have previously reported that transgenic expression of interleukin-4 (IL-4) counterregulates the disease process, completely protecting NOD mice from insulitis and diabetes. Here we demonstrate the presence of autoreactivity but lack of pathogenicity of the IL-4-regulated lymphocytes. The importance of T cell diversity for the protective effect of IL-4 is demonstrated through breeding with transgenic BDC2.5 mice, which have an almost exclusively monoclonal T cell repertoire. Limitation of T cell diversity abrogated the protection by IL-4. We suggest that 'immune deviation' in NOD-IL-4 mice is mediated by the pancreatic tissue itself, which causes activation of distinct, nonpathogenic T cell specificities.

AB - Diabetes in nonobese diabetic (NOD) mice is an autoimmune disease characterized by the destruction of the β cells in the pancreas. We have previously reported that transgenic expression of interleukin-4 (IL-4) counterregulates the disease process, completely protecting NOD mice from insulitis and diabetes. Here we demonstrate the presence of autoreactivity but lack of pathogenicity of the IL-4-regulated lymphocytes. The importance of T cell diversity for the protective effect of IL-4 is demonstrated through breeding with transgenic BDC2.5 mice, which have an almost exclusively monoclonal T cell repertoire. Limitation of T cell diversity abrogated the protection by IL-4. We suggest that 'immune deviation' in NOD-IL-4 mice is mediated by the pancreatic tissue itself, which causes activation of distinct, nonpathogenic T cell specificities.

UR - http://www.scopus.com/inward/record.url?scp=0030879734&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030879734&partnerID=8YFLogxK

U2 - 10.1016/S1074-7613(00)80362-3

DO - 10.1016/S1074-7613(00)80362-3

M3 - Article

VL - 7

SP - 411

EP - 418

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 3

ER -