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 journalArticle

Abstract

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
Volume187
Issue number7
DOIs
StatePublished - Oct 1 2011

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Type 1 Diabetes Mellitus
T-Lymphocytes
Chromogranins
Glucose-6-Phosphatase
Inbred NOD Mouse
Adoptive Transfer
Regulatory T-Lymphocytes
Lymphocyte Activation
Autoimmunity
Homeostasis
Clone Cells
Incidence
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Bettini, M., Szymczak-Workman, A. L., Forbes, K., Castellaw, A. H., Selby, M., Pan, X., ... Vignali, D. A. A. (2011). Cutting edge: Accelerated autoimmune diabetes in the absence of LAG-3. Journal of Immunology, 187(7), 3493-3498. https://doi.org/10.4049/jimmunol.1100714

Cutting edge : Accelerated autoimmune diabetes in the absence of LAG-3. / Bettini, Maria; Szymczak-Workman, Andrea L.; Forbes, Karen; Castellaw, Ashley H.; Selby, Mark; Pan, Xiaoyu; Drake, Charles G.; Korman, Alan J.; Vignali, Dario A A.

In: Journal of Immunology, Vol. 187, No. 7, 01.10.2011, p. 3493-3498.

Research output: Contribution to journalArticle

Bettini, M, Szymczak-Workman, AL, Forbes, K, Castellaw, AH, Selby, M, Pan, X, Drake, CG, Korman, AJ & Vignali, DAA 2011, 'Cutting edge: Accelerated autoimmune diabetes in the absence of LAG-3', Journal of Immunology, vol. 187, no. 7, pp. 3493-3498. https://doi.org/10.4049/jimmunol.1100714
Bettini M, Szymczak-Workman AL, Forbes K, Castellaw AH, Selby M, Pan X et al. Cutting edge: Accelerated autoimmune diabetes in the absence of LAG-3. Journal of Immunology. 2011 Oct 1;187(7):3493-3498. https://doi.org/10.4049/jimmunol.1100714
Bettini, Maria ; Szymczak-Workman, Andrea L. ; Forbes, Karen ; Castellaw, Ashley H. ; Selby, Mark ; Pan, Xiaoyu ; Drake, Charles G. ; Korman, Alan J. ; Vignali, Dario A A. / Cutting edge : Accelerated autoimmune diabetes in the absence of LAG-3. In: Journal of Immunology. 2011 ; Vol. 187, No. 7. pp. 3493-3498.
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