Tracking Donor-Reactive T Cells: Evidence for Clonal Deletion in Tolerant Kidney Transplant Patients Scientists established an assay to identify donor-reactive T cells and test the role of deletion in tolerance after combined kidney and bone marrow transplantation. Using high-throughput sequencing of the T cell receptor B chain CDR3 region, they define a fingerprint of the donor-reactive T cell repertoire before transplantation and track those clones after transplant. [Sci Transl Med] Abstract Mast Cells Form Antibody-Dependent Degranulatory Synapse for Dedicated Secretion and Defense Investigators show that interaction of mast cells with antibody-targeted cells induces the polarized exocytosis of their granules resulting in a sustained exposure of effector enzymes, such as tryptase and ​chymase, at the cell-cell contact site. This previously unidentified mast cell effector mechanism is triggered by both IgE- and IgG-targeted cells. [Nat Commun] Abstract Effector Vγ9Vδ2 T Cells Dominate the Human Fetal γδ T-Cell Repertoire Researchers show that, rather than requiring postnatal microbial exposure, T cells expressing the T-cell receptor containing the γ-chain variable region 9 and the δ-chain variable region 2 (Vγ9Vδ2 T cells) are the predominant blood subset in the second-trimester fetus, whereas Vδ1+ and Vδ3+ γδ T cells are present only at low frequencies at this gestational time. [Proc Natl Acad Sci USA] Abstract Nonapoptotic and Extracellular Activity of Granzyme B Mediates Resistance to Regulatory T Cell (Treg) Suppression by HLA-DR–CD25hiCD127lo Tregs in Multiple Sclerosis and in Response to IL-6 Scientists show that memory CD4+CD127loFOXP3+ Treg subsets do not express granzyme B (GzmB), whereas activated, nonregulatory CD4 T cells isolated from patients with multiple sclerosis express higher levels of GzmB than do cells from healthy donors. [J Immunol] Abstract Soluble Tim-3 Is Shed from CD8+ T Cells by the Sheddase ADAM10, Is Increased in Plasma during Untreated HIV Infection, and Correlates with HIV Disease Progression Investigators show that T cell immunoglobulin mucin domain-3 (Tim-3) is shed from the surface of responding CD8+ T cells by the matrix metalloproteinase, ADAM10, producing a soluble form of the co-inhibitory receptor. Despite previous reports in the mouse model, no alternatively spliced, soluble form of Tim-3 was observed in humans. [J Virol] Abstract Viral Restriction Factor Tetherin Prevents Leucine-Rich Pentatricopeptide Repeat Containing Protein (LRPPRC) from Association with Beclin 1 and B-Cell CLL/Lymphoma 2 (Bcl-2) and Enhances Autophagy and Mitophagy Tetherin has been characterized as a key factor that restricts viral particles such as HIV and hepatitis C virus on plasma membranes, acts as a ligand of immunoglobulin-like transcript 7 receptor in tumor cells, and suppresses antiviral innate immune responses mediated by human plasmacytoid dendritic cells. Scientists show that tetherin not only serves as a substrate of autophagy but itself regulates the initiation of autophagy. [J Biol Chem] Abstract | Full Article Aspartate-β-Hydroxylase Induces Epitope-Specific T Cell Responses in Hepatocellular Carcinoma Investigators observed that aspartate-β-hydroxylase protein and related peptides were highly immunogenic in patients with hepatocellular carcinoma and produce the type of cellular immune responses required for generation of anti-tumor activity. [Vaccine] Abstract Heterogeneous Expansion of CD4+ Tumor-Infiltrating T-Lymphocytes in Clear Cell Renal Cell Carcinomas Researchers utilized deep sequencing of T-cell receptor beta chains, which serve as a unique identifier for each T clonotype, to characterize the CD4+/CD8+ tumor-infiltrating T-lymphocytes repertoire in clear cell renal cell carcinoma patients, assess the diversity and clonality of infiltrated T-cells in distinct tissues from patients and depict the clonal expansion events that occur in anti-tumor immune responses. [Biochem Biophys Res Commun] Abstract Adoptive T-Cell Therapy of Prostate Cancer Targeting the Cancer Stem Cell Antigen EpCAM An EpCAM-specific chimeric antigen receptor (CAR) was constructed to transduce human peripheral blood lymphocytes (PBLs) and thereby enable them to target the cancer stem cell marker EpCAM. Scientists demonstrate that CAR-expressing PBLs can kill a highly metastatic clone of PC3 tumor cells in vitro and in vivo. [BMC Immunol] Abstract | Full Article Subscribe to our sister publications: Immunology of Infectious Disease News and Immune Regulation News! |