TY - JOUR
T1 - Cutting edge
T2 - Accelerated autoimmune diabetes in the absence of LAG-3
AU - Bettini, Maria
AU - Szymczak-Workman, Andrea L.
AU - Forbes, Karen
AU - Castellaw, Ashley H.
AU - Selby, Mark
AU - Pan, Xiaoyu
AU - Drake, Charles G.
AU - Korman, Alan J.
AU - Vignali, Dario A.A.
PY - 2011/10/1
Y1 - 2011/10/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1100714
DO - 10.4049/jimmunol.1100714
M3 - Article
C2 - 21873518
AN - SCOPUS:80053550261
SN - 0022-1767
VL - 187
SP - 3493
EP - 3498
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -