TIGIT expression on CD8+ T cells correlates with higher cytotoxic capacity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA718607 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Persistent exposure to antigen leads to T cell exhaustion and immunologic dysfunction. We examined the immune exhaustion markers TIGIT and PD-1 in HIV-infected and healthy individuals and the relationship with cytotoxic CD8+ T lymphocyte (CTL) activity. Frequencies of TIGIT but not PD-1 positively correlated with CTL activity in HIV-aviremic and healthy individuals; however, there was no correlation in HIV-viremic individuals. Transcriptome analyses revealed upregulation of genes associated with antiviral immunity in TIGIT+ versus TIGIT-CD8+ T cells. Our data suggest that TIGIT+CD8+ T cells do not necessarily represent a state of immune exhaustion and maintain an intrinsic cytotoxicity in HIV-infected individuals.
2021-03-31 | GSE171172 | GEO
Project description:TIGIT+ Tregs suppress Th1 and Th17 responses while sparing Th2 responses. Analysis of global gene expression of TIGIT+ vs. TIGIT- Tregs from naive mice reveled that TIGIT+ Tregs display an activated phenotype and are enriched for Treg signature genes including the Treg effector molecule Fgl2 which enables them to selectively spare Th2 responses. TIGIT+ and TIGIT- Tregs were sorted from naïve Foxp3-GFP KI mice (pooled spleen and lymph nodes) TIGIT: T cell immunoreceptor with Ig and ITIM domains
2014-12-12 | E-GEOD-56299 | biostudies-arrayexpress
Project description: Not available
| S-EPMC8599894 | biostudies-literature
Project description:TIGIT+ Tregs suppress Th1 and Th17 responses while sparing Th2 responses. Analysis of global gene expression of TIGIT+ vs. TIGIT- Tregs from naive mice reveled that TIGIT+ Tregs display an activated phenotype and are enriched for Treg signature genes including the Treg effector molecule Fgl2 which enables them to selectively spare Th2 responses.
2014-12-12 | GSE56299 | GEO
Project description:TIGIT is an immune checkpoint receptor that can signal via its intracellular inhibitory motifs to inhibit T cells, though the mechanisms remain poorly defined. To elucidate inhibitory signalling interactors of TIGIT, proximity proteomics was employed in model Jurkat T cells expressing TIGIT fused to APEX2. This identified several ligation-specific TIGIT interactors, including proteins involved in signalling (Grb2 and SOS1), cytoskeletal (CD2AP and SdcBP), and endocytic processes (IST1 and SNX3). A TIGIT mutant incapable of signalling via its inhibitory motifs prevented the recruitment of these proteins, indicating inhibitory signalling-specific engagement of these pathways. Furthermore, TIGIT engagement with these pathways, in addition to its phosphorylation and internalisation, was dependent on T cell activation as well as TIGIT ligation. Collectively, these findings demonstrate that TIGIT inhibitory signalling is restricted to activated T cells, indicating a regulatory mechanism that limits inhibition to when functionally required.
2025-05-14 | PXD063349 | Pride
Project description:We compared the gene expression in wild type CD4+ T cells stimulated with agonistic anti-TIGIT 4D4 antibody to that of isotype and TIGIT-deficient (KO) controls.
2011-01-01 | E-MEXP-2847 | biostudies-arrayexpress
Project description:B cell depletion in patients with relapsing remitting multiple sclerosis (RRMS) markedly prevents new MRI lesions and disease activity, suggesting the hypothesis that altered B cell function leads to the activation of T cells driving disease pathogenesis. Here, we performed comprehensive analyses of memory B cells from patients with MS and healthy age-matched controls stimulated with CD40L and IL-21, modeling the help of follicular helper T cells (Tfh cells), and found a differential gene expression signature in multiple B cell pathways. Most striking was impaired TIGIT expression on MS-derived B cells mediated by dysregulation of the transcription factor TCF4. Activated circulating Tfh cells (cTfh cells) expressed CD155, the ligand of TIGIT, and TIGIT on B cells revealed their capacity to suppress the proliferation of IL-17-producing cTfh cells via TIGIT/CD155 axis. Finally, CCR6+ cTfh cells were significantly increased in MS and their frequency was inversely correlated with that of TIGIT+ B cells. Together, these data suggest that the dysregulation of negative feedback loops between TIGIT+ memory B cells and cTfh cells in MS drive the activated immune system in the disease.
2022-10-19 | GSE211358 | GEO
Project description:Bladder cancer is a highly metastatic tumor and one of the most common malignant tumors originating in the urinary system. Although the application of immune checkpoint, including programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), achieved definite efficacy, the effect of immunotherapy for bladder cancer is still not very satisfactory. Therefore, it is very urgent to develop new targets to expand the options of immunotherapies. In this study, we utilized single cell sequencing to explore the cell composition and detected a subset of Treg cells with high expression of T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) and interleukin (IL)-32 molecules. Certainly, anti-tumor immune response was suppressed by this subset of Treg cells and IL-32 promoted the bladder cancer metastasis. Nevertheless, targeting TIGIT not only could reverse immunosuppression through restoring anti-tumor immune response mediated by T cells but suppressed the secretion of IL-32 and inhibited the metastasis of bladder cancer cells. Thus, our study provided a novel insight into the immunosuppression in bladder cancer and developed the TIGIT as the novel target for immunotherapy of bladder cancer. Furthermore, we also illustrated mechanism of the dual effect of targeting TIGIT in bladder cancer and revealed the metastasis-promoting effect of IL-32 in bladder cancer. Taken together, the discovery raises the possibility of TIGIT targets against bladder cancer from the bench to the bedside.
2022-01-31 | GSE186520 | GEO
Project description:Antibiotic resistance is a major public health threat, and alternatives to antibiotic therapy are urgently needed. Immunotherapy, particularly the blockade of inhibitory immune checkpoints, is a leading treatment option in cancer and autoimmunity. In this study, we used a murine model of Salmonella Typhimurium infection to investigate whether immune checkpoint blockade could be applied to bacterial infection. We found that the immune checkpoint T-cell immunoglobulin and ITIM domain (TIGIT) was significantly upregulated on lymphocytes during infection, particularly on CD4+ T cells, drastically limiting their proinflammatory function. Blockade of TIGIT in vivo using monoclonal antibodies was able to enhance immunity and improve bacterial clearance. The efficacy of anti-TIGIT was dependent on the capacity of the antibody to bind to Fc (fragment crystallizable) receptors, giving important insights into the mechanism of anti-TIGIT therapy. This research suggests that targeting immune checkpoints, such as TIGIT, has the potential to enhance immune responses toward bacteria and restore antibacterial treatment options in the face of antibiotic resistance. In this experiment, we investigated the effect of TIGIT on CD4+ T cells by performing bulk RNA-sequencing on WT or TIGIT-/- CD4+ T cells in the context of S. Typhimurium infection.
2024-10-31 | GSE234086 | GEO
Project description:To investigate the role of TIGIT in CD4+ T cell differentiation, Total CD4+ T cells were isolated from WT or Tigit -/- mice. Cells were stimulated with anti-CD3/CD28 for 3 d. Cells were then collected and total RNA was extracted.
2025-03-26 | GSE274668 | GEO