Steady-State Production of IL-4 Modulates Immunity in Mouse Strains and Is Determined by Lineage Diversity of iNKT Cells Invariant natural killer T cells (iNKT cells) can produce copious amounts of interleukin 4 (IL-4) early during infection. However, indirect evidence suggests they may produce this immunomodulatory cytokine in the steady state. Through intracellular staining for transcription factors, the authors have defined three subsets of iNKT cells that produced distinct cytokines; these represented diverse lineages and not developmental stages, as previously thought. [Nat Immunol] Abstract Epigenetic Modifications Induced by Blimp-1 Regulate CD8+ T Cell Memory Progression during Acute Virus Infection Scientists found that increased proliferation and survival of Blimp-1-deficient CD8+ T cells resulted from sustained expression of CD25 and CD27 and persistent cytokine responsiveness. Silencing of Il2ra and Cd27 reduced the Blimp-1-deficient CD8+ T cell response. [Immunity] Abstract A Single Peptide-Major Histocompatibility Complex Ligand Triggers Digital Cytokine Secretion in CD4+ T Cells Investigators found that naive T cells, T cell blasts, and memory T cells could all be triggered by a single peptide-major histocompatibility complex (pMHC) to secrete tumor necrosis factor-α and interleukin-2 cytokines with a rate of 1,000, 10,000, and 10,000 molecules/min, respectively, and that additional pMHCs did not augment secretion, indicating a digital response pattern. [Immunity] Abstract Granzyme B Degradation by Autophagy Decreases Tumor Cell Susceptibility to Natural Killer-Mediated Lysis Under Hypoxia Researchers demonstrated that hypoxia impairs breast cancer cell susceptibility to natural killer (NK)-mediated lysis in vitro via the activation of autophagy. This impairment was not related to a defect in target cell recognition by NK cells but to the degradation of NK-derived granzyme B in autophagosomes of hypoxic cells. [Proc Natl Acad Sci USA] Abstract The TNF Family Member 4-1BBL Sustains Inflammation by Interacting with TLR Signaling Components During Late-Phase Activation Toll-like receptor 4 (TLR4)-mediated inflammation, which occurs in two phases, depends on the TNF family member 4-1BB ligand (4-1BBL) to sustain tumor necrosis factor-α (TNF-α) production during late-phase signaling. Scientists showed that Toll-interleukin-1 receptor domain-containing adaptor protein and the kinase IRAK2 interacted with 4-1BBL to mediate late-phase TLR4 signaling. [Sci Signal] Abstract | Press Release IVIg Immune Reconstitution Treatment Alleviates the State of Persistent Immune Activation and Suppressed CD4 T Cell Counts in CVID Researchers addressed the hypothesis that poor antibody-mediated immune control of infections may result in substantial perturbations in the T cell compartment. Newly diagnosed common variable immunodeficiency (CVID) patients were sampled before, and 6-12 months after, initiation of intravenous immunoglobulin (IVIg) therapy. [PLoS One] Full Article Serotonin 5-HT2A Receptor Activation Blocks TNF-α Mediated Inflammation In Vivo Recently, the authors discovered that selective activation of serotonin 5-HT2A receptors with the agonist (R)-DOI produces a super-potent blockade of proinflammatory markers in primary rat aortic smooth muscle cells. Here, they demonstrated that systemic administration of (R)-DOI can block the systemic effects of tumor necrosis factor alpha (TNF-α) in whole animal, with potent anti-inflammatory effects in the aortic arch and small intestine. [PLoS One] Full Article | Press Release Bisphosphonates Target B Cells to Enhance Humoral Immune Responses Investigators showed that the administration of clinically relevant doses of bisphosphonates in mice increases antibody responses to live and inactive viruses, proteins, haptens, and existing commercial vaccine formulations. Bisphosphonates target directly B cells and enhance B cell expansion and antibody production upon antigen encounter. [Cell Rep] Full Article | Graphical Abstract |