IgH Sequences in Common Variable Immune Deficiency Reveal Altered B Cell Development and Selection Common variable immune deficiency (CVID) patients suffer from impaired antibody responses, autoimmunity, and susceptibility to lymphoid cancers. To explore the cellular basis for these clinical phenotypes, researchers conducted high-throughput DNA sequencing of immunoglobulin heavy chain gene rearrangements from 93 CVID patients and 105 control subjects and sorted naïve and memory B cells from 13 of the CVID patients and 10 of the control subjects. [Sci Transl Med] Abstract High-Resolution Analysis of the Human T-Cell Receptor Repertoire Scientists showed that T-cell receptor (TCR) ligation-anchored-magnetically captured PCR (TCR-LA-MC PCR) identifies TCR α- and β-chain diversity without sequence-associated or quantitative restrictions in healthy and diseased conditions. TCR-LA-MC PCR identifies convergent recombination events, classifies different stages of cutaneous T-cell lymphoma in vivo and demonstrates TCR reactivation after in vitro cytomegalovirus stimulation. [Nat Commun] Full Article | Press Release Modeling Human Severe Combined Immunodeficiency and Correction by CRISPR/Cas9-Enhanced Gene Targeting Using severe combined immunodeficiency patient-specific induced pluripotent stem cells and a T cell in vitro differentiation system, researchers demonstrated a complete block in early T cell development of JAK3-deficient cells. Correction of the JAK3 mutation by CRISPR/Cas9-enhanced gene targeting restores normal T cell development, including the production of mature T cell populations with a broad T cell receptor repertoire. [Cell Rep] Full Article | Graphical Abstract Influences of Large Sets of Environmental Exposures on Immune Responses in Healthy Adult Men Six healthy males lived in a closed habitat simulating a spacecraft for 520 days. Investigators measured multiple immune parameters with blood samples at chosen time points after the mission. [Sci Rep] Full Article Increased Expression of Surface CD44 in Hypoxia-DCs Skews Helper T Cells toward a Th2 Polarization The authors previously reported that hypoxia significantly altered dendritic cells (DCs) to a DC2 phenotype and promoted a Th2 polarization of naïve T cells with increased IL-4 production. Here they found the over-expression of surface CD44 in DCs was involved in this process via ligand binding. [Sci Rep] Full Article Interleukin-25 Mediates Transcriptional Control of PD-L1 via STAT3 in Multipotent Human Mesenchymal Stromal Cells (hMSCs) to Suppress Th17 Responses Researchers found that, along with Th1 responses, hMSCs strongly suppressed Th17 responses and this required both interleukin (IL)-25—also known as IL-17E—as well as programmed death ligand-1 (PD-L1), a potent cell surface ligand for tolerance induction. Knockdown of IL-25 expression in hMSCs abrogated Th17 suppression in vitro and in vivo. [Stem Cell Rep] Full Article | Graphical Abstract Stromal Infiltration of CD8 T Cells Is Associated with Improved Clinical Outcome in HPV-Positive Oropharyngeal Squamous Carcinoma Scientists investigated tumor-infiltrating lymphocytes in relation to human papillomavirus (HPV) tumor status and patient survival. HPV-positive compared with HPV-negative oropharyngeal squamous cell carcinoma had higher infiltration in both tumor and stromal areas of CD4 and CD8 T cells but not FoxP3 T regulatory cells. [Br J Cancer] Abstract Caspase-Independent Apoptosis in Infected Macrophages Triggered by Sulforaphane via Nrf2/p38 Signaling Pathways Researchers showed that human THP-1-derived macrophages infected with Mycobacterium abscessus presented an increase in ROS production and cell necrosis. Interestingly, pretreatment of macrophages with sulforaphane, an activator of the antioxidant key regulator Nrf2, followed by M. abscessus infection significantly decreased mycobacterial burden. [Cell Death Discov] Full Article Subscribe to our sister publications: Immunology of Infectious Disease News & Immune Regulation News! |