| First Author | Bettini M | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 7 | Pages | 3493-8 |
| PubMed ID | 21873518 | Mgi Jnum | J:179341 |
| Mgi Id | MGI:5301800 | Doi | 10.4049/jimmunol.1100714 |
| Citation | Bettini M, et al. (2011) Cutting edge: accelerated autoimmune diabetes in the absence of LAG-3. J Immunol 187(7):3493-8 |
| abstractText | 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 A-specific 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. |
