Immunology

Contribution of inhibitory receptor TIGIT to NK cell education

Yuke He, Hui Peng, Rui Sun, Haiming Wei, Hans-Gustaf Ljunggren, Wayn

BTB and CNC homology (BACH) proteins are transcriptional repressors of the basic region leucine zipper (bZIP) transcription factor family. Recent studies indicate widespread roles of BACH proteins in controlling the development and function of the innate and adaptive immune systems, including the differentiation of effector and memory cells of the B and T cell lineages, CD4+ regulatory T cells and macrophages. Here, we emphasize similarities at a molecular level in the cell-type-specific activities of BACH factors, proposing that competitive interactions of BACH proteins with transcriptional activators of the bZIP family form a common mechanistic theme underlying their diverse actions. The findings contribute to a general understanding of how transcriptional repressors shape lineage commitment and cell-type-specific functions through repression of alternative lineage programmes.

Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell–mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (TEM), and longer-lived central memory (TCM) and stem cell memory (TSCM) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7– and IL-15–mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of TCM and TSCM memory cells resulted in phenotypic conversion into TEM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired TEM-associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells.

Selectins guide the traffic of activated T-cells by mediating their tethering and rolling onto inflamed endothelium, acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that may act as E-selectin ligands, and focus our study on comparing the role PSGL-1 (P-selectin glycoprotein ligand-1) and CD43, known E-selectin ligands, to CD44, a ligand not previously described as an E-selectin ligand on activated human T-cells. We showed that CD44 expressed on both CD4+ and CD8+ T-cells acts as a functional E-selectin ligand and thus carries a binding epitope identifying it as HCELL (hematopoietic cell E-/L-selectin ligand). Furthermore, by knocking down these ligands individually or together in primary activated human T-cells, we demonstrated that CD44, and not CD43, co-operates with PSGL-1 as major E-selectin ligands. Additionally, we confirmed the relevance of our findings to chronic autoimmune disease, by showing that CD44 and PSGL-1, but not CD43, from T-cells isolated from psoriasis patients, bind E-selectin.

Post-translational control of T cell development by the ESCRT protein CHMP5

Journal of Immunology Research is a peer-reviewed, Open Access journal that publishes research articles, review articles, as well as clinical studies in all aspects of immunology research.

Natural killer (NK) cells target virally infected and transformed cells for cytolysis. When sufficient activating receptors on the NK cell surface, such as NKG2D, are engaged by ligands on the target cell, such as ULBP proteins, the NK cell kills the target. Polymorphisms within ULBP-encoding genes are associated with immune dysfunction. Zuo et al. found that the affinity of a commonly occurring ULBP6 variant for NKG2D was greater than that of the wild-type protein, which impaired NK cell activation. A soluble form of this protein variant bound so tightly to NKG2D that it suppressed receptor activation and target cell killing in response to other NKG2D ligands. Together, these data suggest that targeting NK cell–ligand interactions may provide therapies to modulate the strength of immune responses.

The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to encourage communication of the very best cancer research from laboratories and clinics in all countries. The breadth of its coverage, its editorial independence and it consistent high standards, have made BJC one of the world's premier general cancer journals. Its increasing popularity is reflected by a steadily rising impact factor.