We find that LKB1 is required for several key metabolic processes in T-cell progenitors. For example, LKB1 controls expression of CD98, a key subunit of the L-system aa transporter and is also required for the pre-TCR to induce and sustain the regulated phosphorylation of the ribosomal S6 subunit, a key regulator of protein synthesis. In the absence of LKB1 TCR-β-selected thymocytes MAPK Inhibitor Library failed to proliferate and did not survive. LBK1 was also required for survival and proliferation of peripheral T cells. These data thus reveal a conserved and essential role for LKB1 in the proliferative responses
of both thymocytes and mature T cells. “
“The mechanisms underlying Japanese encephalitis virus (JEV) pathogenesis need to be thoroughly explored to delineate therapeutic approaches. It is believed that JEV manipulates the innate and adaptive compartments of the host’s immune system to evade Selleckchem GS 1101 immune response and cross the blood–brain barrier. The present study was thus designed to investigate the functional modulation of DCs after exposure to JEV and to assess the consequences on CD4+ T-lymphocyte functions. Human monocyte-derived DCs were either infected with 1 MOI of live virus, UV-inactivated
virus, or were mock-infected. Replication-competent JEV induced a significant increase in the expression of maturation markers 48 h postinfection, along with that of programmed cell death 1 ligand 1 (PD-L1; also called B7-H1 and CD274). JEV-infected DCs expanded the Treg cells in allogenic mixed lymphocyte reactions. The expansion of Treg cells by JEV-infected DCs was
significantly reduced upon blocking PD-L1 using an antagonist. In addition, JEV-infected DCs significantly altered the proliferation and reduced the polarization of Th cells toward the Th1-cell phenotype. The results, for the first time, Amine dehydrogenase suggest that JEV evades the host’s immune system by modulating the crosstalk between DCs and T lymphocytes via the PD-L1 axis. “
“In this study, we elucidated the role of tumor necrosis factor (TNF)-α in the host defense to pulmonary infection with Streptococcus pneumoniae and defined the cellular source of this cytokine at an early stage of infection. Administration of anti-TNF-α monoclonal antibody (mAb) resulted in the reduced accumulation of neutrophils in bronchoalveolar lavage fluids (BALFs) and severe exacerbation of this infection. In a flow cytometric analysis, the intracellular expression of TNF-α was detected in Gr-1bright+ and Gr-1dull+ cells during the time intervals postinfection, and F4/80+ cells expressed intracellular TNF-α before Gr-1dull+ cells appeared. The Gr-1bright+ and Gr-1dull+ cells sorted from BALF cells at 24 h were identified as neutrophils and macrophage-like cells, respectively, and the Gr-1dull+ cells expressing CD11c, partially CD11b and a marginal level of F4/80 secreted TNF-α in in vitro cultures.