Lymphocyte Activation Gene 3 (LAG-3) Modulates the Ability of CD4 T-cells to Be Suppressed In Vivo

• DOI: 10.1371/journal.pone.0109080
• Publication Date: 2014-11-05T19:07:38Z
• Authors: Nicholas M. Durham; Christopher J. Ni...; Christopher M. Ja...; Jimmy Elias; Christina M. Kochel; Robert A. Anders; Charles G. Drake
• Keywords: Homeostasis

Lymphocyte Activation Gene – 3 (LAG-3) is an immune checkpoint molecule that regulates both T-cell activation and homeostasis. However, the molecular mechanisms underlying LAG-3's function are generally unknown. Using a model in which LAG-3 blockade or absence reliably augmented homeostatic proliferation vivo, we found IL-2 STAT5 critical for function. Similarly, was ineffective of regulatory T-cells (Treg), suggesting important role either responsiveness conventional (Tconv) to regulation, relative defect ability KO (Treg) suppress Tconv. In this model, Treg suppressed manner fairly similar wild-type (WT) Treg, but Tconv were relatively resistant suppression. Further studies also identified induction/expansion Treg. Finally, (or knockout) led skewing naïve CD4 toward TH1 phenotype vitro vivo. Together, these data suggest expression on cells makes them more susceptible based suppression, development response.