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Mucosal B cells and their function
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Jo Spencer, Edward N. Janoff, Per Brandtzaeg
Dendritic cells in MALT are exposed to antigens such as bacterial products for presentation to T cells and B cells and may be modified by bacterial products via pattern recognition receptors. T-cell activation induces the upregulation of CD278 (ICOS) and CD154 (CD40L), essential for cognate B-cell–T-cell interactions. This T-cell-dependent mechanism of B-cell activation initiates the formation of germinal centers. The importance of cognate interactions between B and T cells for germinal center formation is supported by the fact that no germinal centers are formed when the CD40–CD154/CD40L interaction is disabled in humans (CD154 mutation in X-linked hyper-IgM syndrome) or in CD40 knockout mice.
Cardiovascular Complications of Immune Checkpoint Inhibitors
Published in Shyam S. Bansal, Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Sultan Tousif, Anand Prakash Singh, Prachi Umbarkar, Hind Lal
The co-stimulatory signal, which regulates the recognition of antigens by the TCR, can also be termed as an immune checkpoint. Immune checkpoints can be either costimulatory or co-inhibitory. CD27, CD37, CD40, GITR (CD278), and OX40 (CD134) are co-stimulatory immune checkpoints that fall under the tumor necrosis factor (TNF) superfamily, whereas CD28 and ICOS stimulatory signals belong to the B7-CD28 superfamily. Programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), adenosine A2A receptor (A2AR), indoleamine 2,3-dioxygenase (IDO), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase isoform 2 (NOX-2), and V-domain Ig suppressor of T cell activation (VISTA) are considered as co-inhibitory immune checkpoints. On exposure to pathogens, adaptive immune cells are activated by antigen presentation and the signals induced by co-stimulatory immune checkpoints to protect the healthy tissues from damage [1]. The inhibitory immune checkpoint competes with the co-stimulatory molecule to diminish host immunity during pathogenic attacks, cancer, or other deadly diseases that hijack the host immune system [2]. This concerted action of co-stimula-tory and inhibitory signals ensures that the immune system does not keep firing once the offending pathogen or disease stimulus has been neutralized. Pathogens and cancer cells have devised smart ways to exploit such inhibitory immune checkpoints to evade host immune response [3, 4]. Therefore, immune checkpoint therapy relies on reactivation of immune function by using either an agonist of the co-stimulatory signal or an antagonist of inhibitory immune checkpoint molecules [5].
Current approaches to evaluate the function of cytotoxic T-cells in non-human primates
Published in Journal of Immunotoxicology, 2023
Cris Kamperschroer, Brendon Frank, Caroline Genell, Hervé Lebrec, Shermaine Mitchell-Ryan, Brigitte Molinier, Courtni Newsome, Marie-Soleil Piche, Daniel Weinstock, Mark Collinge, Wendy Freebern, Daniel Rubio
Flow cytometry has proven to be a robust technology to interrogate immune cell identity and function (O'Hara et al. 2011; van der Strate et al. 2017). After CTL are activated by a target cell expressing the correct peptide-MHC complex, the CTL-mediated killing of target cells occurs via granule-dependent and independent pathways (Trapani and Smyth 2002). Thus, activation of CTL can be measured via a cell degranulation assay (Betts et al. 2003). Degranulation can be determined by the translocation of lysosomal-associated membrane protein 1 [LAMP-1, also known as CD107a], from the lysosomal membrane to the surface of CTL (Figure 2) as well as by release of perforin in cell supernatants. There are markers of CTL activation in addition to CD107a translocation, including expression of T-cell activation surface markers (e.g. CD69, CD25, CD278 [Inducible T-cell COStimulator, ICOS], CD134 [OX40]). When selecting the specific activation markers to monitor, the time between stimulation and analysis needs to also be considered, as some markers are induced earlier after the stimulation (e.g. CD69 up-regulation), while others are induced at later timepoints (e.g. CD25 up-regulation).
Novel immune targets for the treatment of triple-negative breast cancer
Published in Expert Opinion on Therapeutic Targets, 2021
Chiara Corti, Eleonora Nicolò, Giuseppe Curigliano
ICOS/CD278 is a CD28 immunoglobulin superfamily costimulatory molecule that is expressed on activated T cells [79,80]. Besides being expressed on a population of Th1 cytokine producing and tumor antigen-specific effector cells, the absence of ICOS significantly decreases antitumor responses triggered by anti-CTLA4 compounds [81–83]. In this sense, ICOS agonist vopratelimab (JTX-2011) was investigated alone or in combination with anti-PD1 nivolumab in the phase I/II ICONIC clinical trial. Of the 164 patients enrolled, 19 individuals harbored a TNBC diagnosis, showing only one partial response and three disease stabilizations [84]. At present, drug development focusing on metastatic TNBC is investigating KY1044 either alone or in combination with the anti-PD-L1 atezolizumab in a phase 1/2 clinical trial (NCT03829501, Table 1).
Massive parallel screening of phage libraries for the generation of repertoires of human immunomodulatory monoclonal antibodies
Published in mAbs, 2018
Emanuele Sasso, Chiara D’Avino, Margherita Passariello, Anna Morena D’Alise, Daniela Siciliano, Maria Luisa Esposito, Guendalina Froechlich, Riccardo Cortese, Elisa Scarselli, Nicola Zambrano, Alfredo Nicosia, Claudia De Lorenzo
The labeled antibodies APC/Cy7 anti-human CD366 (TIM3), APC/anti-human CD272 (BTLA), APC/anti-human CD137 (4-1BB), PE/anti-human CD134 (OX40), Brilliant Violet 510™/anti-mouse/rat/human CD27, APC/anti-human/mouse/rat CD278 (ICOS), FITC/anti-human TIGIT antibodies were added to each well at a concentration of 10 μg/mL and incubated for 90 minutes at room temperature by gently shaking. After two washes with FACS buffer, the cells were resuspended in PBS and analyzed on CytoFLEX Flow Cytometer (Beckman Coulter).