Cutting edge: Accelerated autoimmune diabetes in the absence of LAG-3

Maria Bettini, Andrea L. Szymczak-Workman, Karen Forbes, Ashley H. Castellaw, Mark Selby, Xiaoyu Pan, Charles G. Drake, Alan J. Korman, Dario A.A. Vignali

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


Lymphocyte activation gene-3 (LAG-3; CD223) is a CD4 homolog that is required for maximal regulatory T cell function and for the control of CD4 + and CD8 + T cell homeostasis. Lag3 -/- NOD mice developed substantially accelerated diabetes with 100% incidence. Adoptive transfer experiments revealed that LAG-3 was primarily responsible for limiting the pathogenic potential of CD4 + T cells and, to a lesser extent, CD8 + T cells. Lag3 -/- mice exhibited accelerated, invasive insulitis, corresponding to increased CD4 + and CD8 + T cell islet infiltration and intraislet proliferation. The frequencies of islet Ag-reactive chromogranin Aspecific CD4 + T cells and islet specific glucose-6-phosphatase- specific CD8 + T cells were significantly increased in the islets of Lag3 -/- mice, suggesting an early expansion of pathogenic clones that is normally restrained by LAG-3. We conclude that LAG-3 is necessary for regulating CD4 + and CD8 + T cell function during autoimmune diabetes, and thus may contribute to limiting autoimmunity in disease-prone environments.

Original languageEnglish (US)
Pages (from-to)3493-3498
Number of pages6
JournalJournal of Immunology
Issue number7
StatePublished - Oct 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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