Aldehyde Dehydrogenase Expression Drives Human Regulatory T Cell Resistance to Posttransplantation Cyclophosphamide Scientists studied early T cell reconstitution in patients undergoing allogeneic blood or marrow transplantation with posttransplantation cyclophosphamide and the effects of mafosfamide, a cyclophosphamide analog, on CD4+ T cells in allogeneic mixed lymphocyte reactions in vitro. [Sci Transl Med] Abstract | Press Release Human Treg Responses Allow Sustained Recombinant Adeno-Associated Virus-Mediated Transgene Expression To determine whether recombinant adeno-associated virus (rAAV) vector expression can persist long term, researchers administered rAAV vectors expressing normal, M-type α-1 antitrypsin (M-AAT) to AAT-deficient subjects at various doses by multiple i.m. injections. M-specific AAT expression was observed in all subjects in a dose-dependent manner and was sustained for more than one year in the absence of immune suppression. [J Clin Invest] Full Article | Press Release Combining Antibody-Directed Presentation of IL-15 and 4-1BBL in a Trifunctional Fusion Protein for Cancer Immunotherapy Scientists propose the combination of IL-15 and 4-1BBL in a single, tumor-directed molecule. Therefore, a trifunctional antibody-fusion protein was generated, composed of a tumor-specific recombinant antibody, IL-15 linked to a fragment of the IL-15Rα chain and the extracellular domain of 4-1BBL. [Mol Cancer Ther] Abstract Glucocorticoid Inhibition of Activation-Induced Cytidine Deaminase Expression in Human B Lymphocytes Researchers demonstrated that physiologic concentrations of glucocorticoids can act on human B lymphocytes through glucocorticoid receptor-mediated mechanisms to diminish the expression of activation-induced cytidine deaminase, a key regulator of humoral immune responses. [Mol Cell Endocrinol] Abstract ApoE Production in Human Monocytes and Its Regulation by Inflammatory Cytokines Investigators studied apoE production in peripheral blood mononuclear cells (PBMC) and analysis was made with a newly developed apoE ELISpot assay. In PBMC, apoE secretion was restricted to monocytes with classical (CD14++CD16−) and intermediate (CD14+CD16+) monocytes being the main producers. [PLoS One] Full Article Measuring T Cell Receptor and T Cell Gene Expression Diversity in Antigen-Responsive Human CD4+ T Cells Researchers developed a methodology for sequencing expressed genes of TCR alpha and beta chains from single cells and applied this to vaccine (tetanus-toxoid)-responsive CD4+ T cells. TCR alpha and beta chains were both successfully sequenced in 1309 of 3038 CD4+ T cells yielding 677 different receptors. [J Immunol Methods] Abstract Homogeneous Expansion of Human T-Regulatory Cells Via Tumor Necrosis Factor Receptor 2 With the goal of producing homogeneous T-regulatory cells (Tregs), the authors developed a novel expansion protocol targeting tumor necrosis factor receptors (TNFR) on Tregs. In in vitro studies, a TNFR2 agonist was found superior to standard methods in proliferating human Tregs into a phenotypically homogeneous population consisting of 14 cell surface markers. [Sci Rep] Full Article
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