T Cell Co-stimulation and Functional Modulation by Innate Signals

Some TLR ligands for TLR2/3/5/7/9 mediate co-stimulation of T cells with TCR triggering to induce cell proliferation and cytokine production. TLR2 particularly mediates co-stimulation promoting differentiation of T helper (Th)1, Th9, and Th17 cells and directly stimulates the effector functions of mouse Th1, Th17, and CD8+ T cells. Nucleic acid (NA) can induce co-stimulation of T cells, leading to Th2 cell differentiation. Co-stimulation of T cells with STING ligands induces cell growth inhibition by inhibiting mammalian target of rapamycin complex 1 (mTORC1) signals and simultaneously stimulates type I IFN responses through the sustained activation of interferon regulatory factor 3 (IRF3) and TCR-induced mTORC1 activation in mice. Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs), play a pivotal role in the initiation of innate immune responses. Certain PRRs are also expressed by CD4+ and CD8+ T cells, where they function to provide co-stimulatory signals for their activation and differentiation. Recently, stimulator of interferon genes (STING) was found to be highly expressed in CD4+ and CD8+ T cells and to modulate T cell function. STING signaling inhibits cell growth and stimulates type I interferon (IFN-I) responses in T cells through reciprocal regulation between T cell receptor (TCR) and STING signals. Here, we propose a model whereby innate signals by TLRs and STING regulate TCR signals and T cell functions. Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs), play a pivotal role in the initiation of innate immune responses. Certain PRRs are also expressed by CD4+ and CD8+ T cells, where they function to provide co-stimulatory signals for their activation and differentiation. Recently, stimulator of interferon genes (STING) was found to be highly expressed in CD4+ and CD8+ T cells and to modulate T cell function. STING signaling inhibits cell growth and stimulates type I interferon (IFN-I) responses in T cells through reciprocal regulation between T cell receptor (TCR) and STING signals. Here, we propose a model whereby innate signals by TLRs and STING regulate TCR signals and T cell functions. genetically based autoimmune disease characterized by DNA-triggered type I interferonopathy. recycling process in which the cell degrades damaged, redundant, or dangerous cellular organelles and proteins in lysosomes. recombinant chimeric receptors that combine antigen-binding and T cell activation function in a single receptor. CD19-CAR recognizes CD19 on tumors and exhibits cytotoxicity against tumor in a non-MHC restricted manner. endogenous molecules usually sequestered within intracellular compartments of healthy cells but are released upon pathological damage. T cell status represented by loss of effector functions (cytokine secretion, proliferation, and cytotoxicity) due to prolonged antigen stimulation, chronic viral infection, and cancer. rare hereditary form of SLE, characterized by cutaneous lupus with prominent skin manifestations in acral parts of the body. specialized subpopulation of T cells playing a central role in the maintenance of peripheral self-tolerance and immune homeostasis. Whereas the suppressive function of FoxP3+ Treg cells is mainly cell contact-dependent, that of LAP+ Treg cells is both cell contact- and soluble factor-dependent. cytosolic protein complex that induces the activation of Caspase-1, leading to the processing and subsequent release of active proinflammatory cytokines such as IL-1β and IL-18. lipid-based transfection technology; here, describes the delivery of nucleic acids and STING agonist CDNs into cells. extracellular loosed chromatin fibers decorated with antimicrobial proteins released from neutrophil to trap and kill microbes. type of neutrophil death occurring with the release of NETs. MHC class I-restricted TCR that specifically recognizes OVA. highly conserved microbial structures or products. negative co-stimulatory receptors that inhibit T cell activation and contribute to inducing T cell exhaustion. systemic inflammatory disease characterized by vasculopathic lesions that affect the lung and skin. SAVI patients have gain-of-function mutations in STING.