Interleukin-10 precipitates disease in nonobese diabetic mice via a CD8+ T cell-dependent, CD4+ T cell-independent pathway

B. Balasa, J. D. Davies, J. Lee, Nora E Sarvetnick

Research output: Contribution to journalArticle

Abstract

IL-10 has been found essential for an early phase of diabetes in nonobese diabetic (NOD) mice, but later becomes dispensable or even protective against its development. However, the mechanism by which IL-10 mediates the pathway to diabetes in these mice is unknown. In this study, we dissected the cellular components and costimulation pathways required for the acceleration of diabetes in transgenic (tg) NOD mice that express IL-10 in their pancreatic islets (IL-10-NOD mice). Depletion of CD8+ T cells by treatment with the corresponding mAb dramatically inhibited diabetes demonstrating a critical role for CD8+ T cells in this tg mouse model. Treatment with anti CD4 mAb had no such effect. Additionally, administration of mAb to CD40L, B7-2, or ICAM-1 costimulatory molecules, which previously blocked diabetes in NOD mice, did not prevent diabetes in IL-10-NOD mice, indicating that these mice require neither CD28/B7, CD40/CD40L, nor LFA-ICAM-1 interactions for the initiation of this disease. Although hsp65 intensified the proliferation of splenocytes from IL-10-NOD mice in vitro, intraperitoneal immunization of these mice with complete Freund's adjuvant had no effect on their diabetes. We conclude that IL-10 contributes to the pathology of diabetes in NOD mouse early in the disease process via a CD8+ T lymphocyte-dependent pathway without a requirement for CD4+ T cells and the established costimulation pathways. Our findings explain the observed dichotomy of IL-10's effects during the early and late phases of diabetes.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

Fingerprint

Inbred NOD Mouse
T-cells
Medical problems
interleukin-10
Interleukin-10
Precipitates
diabetes
T-lymphocytes
T-Lymphocytes
mice
CD40 Ligand
Intercellular Adhesion Molecule-1
Transgenic Mice
Lymphocyte Function-Associated Antigen-1
Immunization
Freund's Adjuvant
genetically modified organisms
Islets of Langerhans
Pathology
islets of Langerhans

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Interleukin-10 precipitates disease in nonobese diabetic mice via a CD8+ T cell-dependent, CD4+ T cell-independent pathway. / Balasa, B.; Davies, J. D.; Lee, J.; Sarvetnick, Nora E.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

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