Increased islet antigen presentation leads to type-1 diabetes in mice with autoimmune susceptibility

Valeria Judkowski, Michelle Krakowski, Enrique Rodriguez, Lorraine Mocnick, Pere Santamaria, Nora Sarvetnick

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is frequently used in preclinical and clinical protocols to modulate autoimmune responses, bone marrow transplants, and recovery from immune ablative therapies. The immunological outcome of such therapies is not fully understood. We tested the hypothesis that GM-CSF would enhance the maturation of antigen-presenting cells, facilitating presentation of β-cell autoantigens to autoreactive T cells. We found that islet expression of GM-CSF greatly enhanced disease in male mice. Islet-derived APC but not splenic APC showed markedly enhanced capacity to stimulate in vitro proliferative responses of islet-antigen-specific autoreactive T cells. In vivo transfer of CD8+ and CD4+ T cells demonstrate that autoreactive T cells undergo extensive division in pancreatic lymph nodes of GM-CSF-transgenic mice compared with wild-type NOD male mice. Together, the results presented here demonstrate that expression of GM-CSF in the pancreas can enhance autoimmunity in disease-susceptible mice.

Original languageEnglish (US)
Pages (from-to)1031-1040
Number of pages10
JournalEuropean Journal of Immunology
Volume34
Issue number4
DOIs
StatePublished - Apr 2004
Externally publishedYes

Keywords

  • Antigen presentation
  • Diabetes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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