The Role of Gamma Interferon‐Inducible Lysosomal Thiol Reductase (GILT) in T‐cell Activation

IFN‐gamma inducible lysosomal thiol reductase is an intracellular protein whose function is related to antigen presenting cells (APCs) where it plays a crucial role in unfolding the antigenic proteins as well as in the process of invariant chain degradation and stabilization of MHC class II. Based on the literature showing that GILT was present in phylogenetically distant species that lack antigenic processing and MHC class II presentation, as well as the fact that GILT is present in different tissues other than APCs, we decided to look for its potential presence in T lymphocytes. In a series of experiments, we confirmed the presence of GILT within both naïve and activated T lymphocytes. More importantly, by comparing T cell activation of GILT in wild type and GILT knockout mice we found that GILT is not a bystander protein within T lymphocytes, but its presence influences the genuine function of T cells. Surprisingly, we found that GILT suppresses the activity of T lymphocytes. This experimental model will allow us to dissect how a molecule primarily located in the lysosome may affect cytoplasmic and/or nuclear events leading to T cell activation.