The9.3 monoclonal antibody reacts with human CD28，a45kDa costimulatory receptor and a member of the Ig superfamily.CD28is expressed by thymocytes，most peripheral T cells，and NK cells.CD28is a receptor forCD80（B7-1）and CD86（B7-2）。Signaling through CD28augments IL-2and IL-2receptor expression as well as cytotoxicity of CD3-activated T cells.The9.3 antibody has been shown to stimulate the proliferation of human T cellsin vitro。
Huang，X.，et al.（2021）。“DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation”Nat Nanotechnol16（2）：214-223。PubMed
Biomaterials can improve the safety and presentation of therapeutic agents for effective immunotherapy，and a high level of control over surface functionalization is essential for immune cell modulation.Here，we developed biocompatible immune cell-engaging particlesn loading。To improve the safety of chimeric antigen receptor（CAR）T cell therapies，micrometre-sized ICEp were injected intratumorally to present a priming signal for systemically administered AND-gate CAR-T cells.Locally retained ICEp presenting a high density of priming antigens activated CAR T cells，driving local tumour clearance while sparing uninjected tuurs immunotrice成本单位ry ligands（anti-CD3and anti-CD28antibodies）and the surface presentation of a cytokine（IL-2）on ICEp were shown to substantially impact human primary T cell activation phenotypes。This modular and versatile biomaterial functionalization platform can provide new opportunities for immunotherapies。
in vitroT cell stimulation/activation
Koh，J.，et al.（2020）。“MDSC subtypes and CD39expression on CD8（+）T cells predict the efficacy of anti-PD-1immunotherapy in patients with advanced NSCLC”Eur J Immunol50（11）：1810-1819。PubMed
The major suppressive immune cells in tumor sites are myeloid derived suppressor cells（MDSCs），tumor-associated macrophages（TAMs），and Treg cells，and the major roles of these suppressive immune cells include hindering T-cell activities and supporting tumor progression and survival.In this study，we analyzed the pattern of circulating MDSC subtypes in patients with non-small cell lung cancer引导到poor clinical outcomes。First，we verified PMN-MDSCs，monocytic-MDSCs（M-MDSCs），and Treg cells increased according to the stages of NSCLC，and MDSCs effectively suppressed T-cell activities and induced T-cell exhaustion.The analysis of NSCLC patients treated with anti-PD-1 immunotherapy demonstrated that low PMN-MDSCs，M-MDSCs，and CD39（+）CD8T cells asan individual and all together were associated with longer progression free survival and overal survival，suggesting PMN-MDSCs，M-MDSCs，and CD39（+）CD8（+）T cells frequencies in peripheral blood might be useful as potential predictive and prognostic biomarkers。
in vitroT cell stimulation/activation
Hill，E.V.，et al.（2015）。“Glycogen synthase kinase-3 controls IL-10expression in CD4（+）effector T-cell subsets through epigenetic modification of the IL-10promoter”Eur J Immunol45（4）：1103-1115。PubMed
The serine/threonine kinase glycogen synthase kinase-3（GSK3）plays an important role in balancing pro-andanti-inflammatory cytokines。We have examined the role of GSK3in production of IL-10by subsets of CD4（+）Thelper cells。Treatment of naive murine CD4（+）T cells with GSK3inhibitors did not affect their production of IL-10。However，treatment of Th1and Th2cells with GSK3inhibitors dramatically increased production of IL-10.GSK3inhibition also led to upregulation of IL-10among Th1，Th2，and Th17subsets isolated from human blood.The encephalitogenic potential of GSK3inhibitor treatemurind Thcigns制动制动制动开关bian IL-10-dependent mechanism.Analysis of the murine IL-10 promoter in response to inhibition of GSK3in Th1 cells showed modification to atranscriptionally active state indicated by changes in histone H3acetylation and methylation.Additionally，GSK3inhibition increased expression of the transcription factors and Macts and Matrival and ating with the increase in IL-10.These findings are important in the context of autoimmune disease since they show that it is possible to reprogram disease-causing cells through GSK3inhibition。
in vitroT cell stimulation/activation
Bushkin，Y.，et al.（2015）。“Profiling T cell activation using single-molecule fluorescence in situ hybridization and flow cytometry”J Immunol194（2）：836-841。PubMed
Flow cytometric characterization of Ag-specific T cells typically relies on detection of protein analytes.Shifting the analysis to detection of RNA would provide several significant advantages，which we illustrate bydeveloping anew host immunity-based platform for detection of infection of infection m.Cytokine mRN in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in stimulation with pathogen-specific Ags are detected in T cells with single-molecule fluorescence in situ hybridization followed by flow cytometry.Background from pre-existingin vivoanalytes is lower for RNAs than for proteins，allowing greater sensitivity for detection of low-frequency cells.Moreover，mRNA analysis reveals kinetic differences in cytokine expression that apparent at the protein levelbut provide novel insights into gene expression programs expected to fine differents Thebsrobing immunological memory of infections is demonstrated by detecting T cells that recognize mycobacterial and viral Ags in donors exposed to the respective pathogens。
in vitroT cell stimulation/activation
Kovacs，B.，et al.（2005）。“Ligation of CD28by its natural ligand CD86in the absence of TCR stimulation induces lipid raft polarization in human CD4T cells”J Immunol175（12）：7848-7854。PubMed
Stimulation of resting CD4T cells with anti-CD3/CD28-coated beads leads to rapid polarization of lipid rafts（LRs）。It has been postulated that a major role of costimulation is to facilitate LR aggregation.CD86 is up-regulated or expressed aberrantly on immune cells in a wide array of autoimmune and infectious diseases.Using an Ig fusion with the extracellular domain of CD86（CD86Ig）bound to a magnetic bead k562，excells，we demonstrated that ligation of CD28by its natural ligand，but not by Ab，induced polarization of LRs at the cell-bead interface of fresh human CD4T cells in the absence of TCR ligation.This correlated with activation of Vav-1，increase of the intracelllular calcium concentration，and nucletranslation of NFlocation of t result intcell proliferation or cytokine production.These studies show，for the first time，that LR polarization can occur in the absence of TCR triggering，driven solely by the CD28/CD86 interaction.This result has implications for mechanisms of T cell activation.Abnormalities in this process may alter and cell tolerance and suptionsfection。
