High-Vacuum Drainage System in Percutaneous Image-Guided Thoracocentesis for Complex Pleural Effusions

Purpose Our retrospective study is aimed to analyze the efficacy and outcomes between high-vacuum suction drain (HVSD) over passive drainage in the setting of percutaneous image-guided thoracocentesis, with a secondary aim to determine if preprocedural computed tomography (CT) can aid decision-making

Themis-associated phosphatase activity controls signaling in T cell development

Thymocyte-expressed molecule involved in selection (Themis) has been shown to be important for T cell selection by setting the threshold for positive versus negative selection. Themis interacts with the protein tyrosine phosphatase (PTP) Src-homology domain containing phosphatase-1 (Shp1), a negative regulator of the T cell receptor (TCR) signaling cascade. However, how Themis regulates Shp1 is still not clear. Here, using a very sensitive phosphatase assay on ex vivo thymocytes, we have found that Themis enhances Shp1 phosphatase activity by increasing its phosphorylation. This positive regulation of Shp1 activity by Themis is found in thymocytes, but not in peripheral T cells. Shp1 activity is modulated by different affinity peptide MHC ligand binding in thymocytes. Themis is also associated with phosphatase activity, due to its constitutive interaction with Shp1. In the absence of Shp1 in thymocytes, Themis interacts with Shp2, which leads to almost normal thymic development in Shp1 conditional knockout (cKO) mice. Double deletion of both Themis and Shp1 leads to a thymic phenotype similar to that of Themis KO. These findings demonstrate unequivocally that Themis positively regulates Shp1 phosphatase activity in TCR-mediated signaling in developing thymocytes.status: publishe

Lck bound to coreceptor is less active than free Lck

10.1073/pnas.1913334117PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA1172715809-1581

Themis-associated phosphatase activity controls signaling in T cell development

10.1073/pnas.1720209115PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA11548E11331-E1134

Lck bound to coreceptor is less active than free Lck

Src family kinase Lck plays critical roles during T cell development and activation, as it phosphorylates the TCR/CD3 complex to initiate TCR signaling. Lck is present either in coreceptor-bound or coreceptor-unbound (free) forms, and we here present evidence that the two pools of Lck have different molecular properties. We discovered that the free Lck fraction exhibited higher mobility than CD8α-bound Lck in OT-I T hybridoma cells. The free Lck pool showed more activating Y394 phosphorylation than the coreceptor-bound Lck pool. Consistent with this, free Lck also had higher kinase activity, and free Lck mediated higher T cell activation as compared to coreceptor-bound Lck. Furthermore, the coreceptor-Lck coupling was independent of TCR activation. These findings give insights into the initiation of TCR signaling, suggesting that changes in coreceptor-Lck coupling constitute a mechanism for regulation of T cell sensitivity.This research was supported by the Singapore Ministry of Health’s National Medical Research Council under its CBRG/0097/2015 and by Singapore Ministry of Education’s Grant 2014-T2-1-136

Expansion of an Unusual Virtual Memory CD8+ Subpopulation Bearing V?3.2 TCR in Themis-Deficient Mice

10.3389/fimmu.2021.644483Frontiers in Immunology1264448

Targeting car to the peptide?mhc complex reveals distinct signaling compared to that of tcr in a jurkat t cell model

10.3390/cancers13040867Cancers1341-1

Hybrid structural modeling of alloantibody binding to human leukocyte antigen with rapid and reproducible cross-linking mass spectrometry

10.1016/j.crmeth.2023.100569CELL REPORTS METHODS3

Utilizing distinct CAR and TCR signaling to generate enhanced cellular immunotherapy

10.4049/jimmunol.208.Supp.122.02The Journal of Immunology208