Regulation of peanut-specific CD8+ T cells from nonallergic individuals.
Ontology highlight
ABSTRACT:
SUBMITTER: Yu W
PROVIDER: S-EPMC7855141 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Opioid peptides are released at sites of injury, and their cognate G protein-coupled opioid receptors (OR) are expressed on immune cells. Exposure of human circulating CD8+ T cells to selective OR agonists differentially regulates thousands of genes. Gene set enrichment analysis reveals that μ-OR more strongly regulates cellular processes than δ-OR. In TCR naive T cells, triggering μ-OR exhibits stimulatory and inhibitory patterns, yet when administered prior to TCR cross-linking, a μ-OR agonist inhibits activation. μ-OR, but not δ-OR, signaling is linked to upregulation of lipid, cholesterol, and steroid hormone biosynthesis, suggesting lipid regulation is a mechanism for immune suppression. Lipid rafts are cholesterol-rich, liquid-ordered membrane domains that function as a nexus for the initiation of signal transduction from surface receptors, including TCR and μ-OR. We therefore propose that μ-OR-specific inhibition of TCR responses in human CD8+ T cells may be mediated through alterations in lipid metabolism and membrane structure.
| S-EPMC8236285 | biostudies-literature
Project description:Long-term memory T cells have not been well analyzed in individuals vaccinated with a COVID-19 vaccine although analysis of these T cells is necessary to evaluate vaccine efficacy. Here, investigate HLA-A*24:02-restricted CD8+ T cells specific for SARS-CoV-2-derived spike (S) epitopes in individuals immunized with the BNT162b2 mRNA vaccine. T cells specific for the S-QI9 and S-NF9 immunodominant epitopes have higher ability to recognize epitopes than other epitope-specific T cell populations. This higher recognition of S-QI9-specific T cells is due to the high stability of the S-QI9 peptide for HLA-A*24:02, whereas that of S-NF9-specific T cells results from the high affinity of T cell receptor. T cells specific for S-QI9 and S-NF9 are detectable >30 weeks after the second vaccination, indicating that the vaccine induces long-term memory T cells specific for these epitopes. Because the S-QI9 epitope is highly conserved among SARS-CoV-2 variants, S-QI9-specific T cells may help prevent infection with SARS-CoV-2 variants.
| S-EPMC9447987 | biostudies-literature
Project description:APCs are essential for the orchestration of antitumor T cell responses. Batf3-lineage CD8α+ and CD103+ dendritic cells (DCs), in particular, are required for the spontaneous initiation of CD8+ T cell priming against solid tumors. In contrast, little is known about the APCs that regulate CD8+ T cell responses against hematological malignancies. Using an unbiased approach, we aimed to characterize the APCs responsible for regulating CD8+ T cell responses in a syngeneic murine leukemia model. We show with single-cell resolution that CD8α+ DCs alone acquire and cross-present leukemia Ags in vivo, culminating in the induction of leukemia-specific CD8+ T cell tolerance. Furthermore, we demonstrate that the mere acquisition of leukemia cell cargo is associated with a unique transcriptional program that may be important in regulating tolerogenic CD8α+ DC functions in mice with leukemia. Finally, we show that systemic CD8α+ DC activation with a TLR3 agonist completely prevents their ability to generate leukemia-specific CD8+ T cell tolerance in vivo, resulting instead in the induction of potent antileukemia T cell immunity and prolonged survival of leukemia-bearing mice. Together, our data reveal that Batf3-lineage DCs imprint disparate CD8+ T cell fates in hosts with solid tumors versus systemic leukemia.
| S-EPMC6444187 | biostudies-literature
Project description:BackgroundAllergen-specific IgE production is a hallmark of allergic asthma/rhinitis/eczema. Theoretically this could be due to a high number of allergen-specific B cells or allergen-specific T cells helping allergen-specific B cells differentiate into IgE-producing plasma cells. Here, we determined whether the number of allergen-specific B cells or T helper (Th) cells is higher in allergic individuals compared to nonallergic individuals.MethodsA total of 52 allergic individuals and 32 nonallergic individuals were studied. The allergen-specific B and Th cells were enumerated by culturing CFSE-loaded blood mononuclear cells for 7-days with allergen (cat, Timothy or birch), and determining the number of proliferating B or Th cells (diluting CFSE) by flow cytometry. Allergen-specific IgE concentration was determined by fluorescent enzymoimmunoassay (FEIA).ResultsThe quantities of proliferating Th cells but not proliferating B cells specific for cat, Timothy and birch were significantly higher in cat-, Timothy- and birch-allergic individuals compared to nonallergic individuals. The titer of allergen-specific IgE showed significant correlation with allergen-specific Th cells and not with allergen-specific B cells for all 3 allergens.ConclusionsA high number of allergen-specific proliferating Th cells, but not proliferating B cells, may play a role in the pathogenesis of allergic asthma/rhinitis/eczema.
| S-EPMC3102632 | biostudies-literature
Project description:Immune checkpoint blockade (ICB) has revolutionized cancer therapy, but varying response rates illustrate the need for biomarkers of response. Studies in mice have identified a subset of CD8 T cells that is essential for response to PD-1 ICB. These CD8 T cells co-express CXCR5, PD-1 and Tcf1, and provide effector T cells upon PD-1 ICB. It is unknown whether similar T cells play a role in PD-1 ICB in humans. We studied human peripheral blood and lymph nodes (LNs) for the frequency, phenotype, and functionality of CXCR5+ PD-1+ CD8 T cells. We find that CXCR5+ PD-1+ CD8 T cells are memory-like cells, express Tcf1, and lack expression of effector molecules. CXCR5+ PD-1+ CD8 T cells produce cytokines upon stimulation, but have limited proliferative capacity. We studied patients with hematologic malignancies with varying response rates to PD-1 ICB. Specifically in chronic lymphocytic leukemia, in which PD-1 ICB does not induce clinical responses, CXCR5+ PD-1+ CD8 T cells show loss of the memory phenotype and increased effector differentiation. In conclusion, we identified CXCR5+ PD-1+ CD8 T cells in human peripheral blood and LN, which could play a similar role during PD-1 ICB. Future studies should analyze CXCR5+ PD-1+ CD8 T cells during PD-1 ICB and their importance for therapeutic response.
| S-EPMC7984320 | biostudies-literature
Project description:Triple-negative breast cancer (TNBC) highly infiltrated with CD8+ tumor-infiltrating lymphocytes (TIL) has been associated with improved prognosis. This observation led us to hypothesize that CD8+ TIL could be utilized in autologous adoptive cell therapy for TNBC, although this concept has proven to be challenging, given the difficulty in expanding CD8+ TILs in solid cancers other than in melanoma. To overcome this obstacle, we used an agonistic antibody (urelumab) to a TNFR family member, 4-1BB/CD137, which is expressed by recently activated CD8+ T cells. This approach was first utilized in melanoma and, in this study, led to advantageous growth of TILs for the majority of TNBC tumors tested. The agonistic antibody was only added in the initial setting of the culture and yet favored the propagation of CD8+ TILs from TNBC tumors. These expanded CD8+ TILs were capable of cytotoxic functions and were successfully utilized to demonstrate the presence of immunogenic mutations in autologous TNBC tumor tissue without recognition of the wild-type counterpart. Our findings open the way for a successful adoptive immunotherapy for TNBC. Cancer Immunol Res; 5(6); 439-45. ©2017 AACR.
| S-EPMC5525328 | biostudies-literature
Project description:Personalized cancer vaccines are a promising approach for inducing T cell immunity to tumor neoantigens. Using a self-assembling nanoparticle vaccine that links neoantigen peptides to a Toll-like receptor 7/8 agonist (SNP-7/8a), we show how the route and dose alter the magnitude and quality of neoantigen-specific CD8+ T cells. Intravenous vaccination (SNP-IV) induced a higher proportion of TCF1+PD-1+CD8+ T cells as compared to subcutaneous immunization (SNP-SC). Single-cell RNA sequencing showed that SNP-IV induced stem-like genes (Tcf7, Slamf6, Xcl1) whereas SNP-SC enriched for effector genes (Gzmb, Klrg1, Cx3cr1). Stem-like cells generated by SNP-IV proliferated and differentiated into effector cells upon checkpoint blockade, leading to superior antitumor response as compared to SNP-SC in a therapeutic model. The duration of antigen presentation by dendritic cells controlled the magnitude and quality of CD8+ T cells. These data demonstrate how to optimize antitumor immunity by modulating vaccine parameters for specific generation of effector or stem-like CD8+ T cells.
| S-EPMC7746638 | biostudies-literature
Project description:BackgroundArterial stiffness is a well-known predictor of future cardiovascular events. Search for the underlying mechanism of arterial stiffening is still under way. We investigated the relationship between arterial stiffness and cytomegalovirus infection in terms of T-cell senescence.Methods and resultsArterial stiffness was evaluated using pulse wave velocity measurements in 415 Koreans (age 59±12 years). We also investigated the frequency of CD57+ or CD28null senescent T cells in peripheral blood lymphocytes and analyzed which immune parameters were correlated with pulse wave velocity. Furthermore, cytomegalovirus-specific T cells were stimulated with overlapping peptides covering pp65 protein, and T-cell function was evaluated by intracellular cytokine staining of interferon-?, tumor necrosis factor-?, and CD107a. In a multivariate analysis, it was found that the frequency of CD57+ cells in the CD8+ T-cell subset was independently correlated with pulse wave velocity after adjusting for traditional cardiovascular risk factors such as age, sex, diabetes mellitus history, smoking history, body mass index, blood pressure, serum creatinine, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. Cytomegalovirus pp65-specific T cells were more frequently observed in the CD8+CD57+ population than in the CD8+CD57- population, and multivariate analysis revealed that the frequency of cytomegalovirus pp65-specific interferon-?+, tumor necrosis factor-?+, or CD107a+ cells in the CD8+ T-cell subset was independently correlated with pulse wave velocity as well.ConclusionsWe demonstrate that arterial stiffness is associated with senescent CD57+ T cells and CMV pp65-specific T cells in the CD8+ T-cell subset. The precise role of cytomegalovirus-specific, senescent T cells in vascular aging needs to be further investigated.
| S-EPMC5634298 | biostudies-literature
Project description:HIV-specific CD8+ T cells are known to play a key role in viral control during acute and chronic HIV infection. Although many studies have demonstrated the importance of HIV-specific CD8+ T cells in viral control, its correlation with protection against HIV infection remains incompletely understood. To better understand the nature of the immune response that contributes to the early control of HIV infection, we analyzed the phenotype, distribution and function of anti-viral CD8+ T cells in a cohort of HIV-exposed seronegative (HESN) women, and compared them with healthy controls and HIV-infected individuals. Further, we evaluated the in vitro viral inhibition activity of CD8+ T cells against diverse HIV-1 strains. We found that the HESN group had significantly higher levels of CD8+ T cells that express T-stem cell-like (TSCM) and follicular homing (CXCR5+) phenotype with more effector like characteristics as compared to healthy controls. Further, we observed that the HESN population had a higher frequency of HIV-specific poly-functional CD8+ T cells with robust in vitro virus inhibiting capacity against different clades of HIV. Overall, our results demonstrate that the HESN population has elevated levels of HIV-specific poly-functional CD8+ T cells with robust virus inhibiting ability and express elevated levels of markers pertaining to TSCM and follicular homing phenotype. These results demonstrate that future vaccine and therapeutic strategies should focus on eliciting these critical CD8+ T cell subsets.
| S-EPMC8056154 | biostudies-literature
Project description:Mast cells (MCs), strategically localized at mucosal surfaces, provide first-line defense against pathogens and shape innate and adaptive immune responses. Recent studies have shown that MCs are involved in pathogenic responses to several viruses including herpes simplex viruses, dengue virus, vaccinia virus and influenza virus. However, the underlying mechanisms of MCs in the activation of CD8+ T cells during viral infections are not fully understood. Therefore, we investigate the role of MCs in the development of virus-specific CD8+ T cell responses using the well-characterized murine lymphocytic choriomeningitis virus (LCMV) model and the transgenic MasTRECK mice that contain the human diphtheria toxin receptor as an inducible MC-deficient model. Here, we report that MCs are essential for the activation and expansion of virus-specific CD8+ T cells. After MC depletion and subsequent intradermal LCMV infection, the CD8 + T cell effector phenotype and antiviral cytokine production were impaired at the peak of infection (day 8 p.i.). Importantly, MC-deficient mice were unable to control the infection and exhibited significantly higher viral loads in the spleen and in the ear draining lymph nodes compared to that of wild type control mice. In the absence of MCs, dendritic cell (DC) activation was impaired upon LCMV infection. In addition, type-I interferon (IFN) levels in the serum and in the spleen of MC-deficient mice were reduced during the first days of infection. Interestingly, depletion of MCs after intradermal LCMV infection did not impair virus-specific CD8+ T cell expansion, activation or antiviral cytokine production. In summary, our results indicate that MCs play a pivotal role in the activation and antiviral functions of CD8+ T cells through proper DC activation. A better understanding of the impact of MCs on CD8+ T cell responses is mandatory to improve antiviral immune responses.
| S-EPMC8236703 | biostudies-literature