| First Author | Workman CJ | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 2 | Pages | 688-95 |
| PubMed ID | 15634887 | Mgi Jnum | J:95840 |
| Mgi Id | MGI:3527388 | Doi | 10.4049/jimmunol.174.2.688 |
| Citation | Workman CJ, et al. (2005) Negative regulation of T cell homeostasis by lymphocyte activation gene-3 (CD223). J Immunol 174(2):688-95 |
| abstractText | Lymphocyte homeostasis is a central biological process that is tightly regulated. However, its molecular and cellular control is poorly understood. We show that aged mice deficient in lymphocyte activation gene 3 (LAG-3), an MHC class II binding CD4 homologue, have twice as many T cells as wild-type controls. CD4(+) and CD8(+) LAG-3-deficient T cells showed enhanced homeostatic expansion in lymphopenic hosts, which was abrogated by ectopic expression of wild-type LAG-3, but not by a signaling-defective mutant. In addition, in vivo treatment with anti-LAG-3 mAb resulted in enhanced T cell expansion to a level comparable to that in LAG-3-deficient cells. This deregulation of T cell homeostasis also resulted in the expansion of multiple cell types, including B cells, macrophages, granulocytes, and dendritic cells. Lastly, regulatory T cells were dependent on LAG-3 for their optimal control of T cell homeostasis. Our data suggest that LAG-3 negatively regulates T cell homeostasis by regulatory T cell-dependent and independent mechanisms. |
