Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA335704 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes
| PRJNA338813 | ENA
Project description:Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (whole blood RNA-seq)
| PRJNA338797 | ENA
Project description:Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (bulk RNA-seq of sorted CD8+ T-cells)
| PRJNA338796 | ENA
Project description:Teplizumab is approved for delay of diagnosis of type 1 diabetes and may modulate new onset disease. Compared to EBV seronegative patients, those who were EBV seropositive prior to treatment had a more robust response to drug in two clinical trials. We compared the phenotypes, transcriptomes, and development of peripheral blood cells before and after teplizumab treatment. Higher number of Tregs and partially exhausted CD8+ T cells were found in EBV seropositive individuals at the baseline in the TN10 and AbATE trials. Single cell transcriptomics and functional assays identified downregulation of NFkB and other pathways after treatment in treated EBV seropositive patients. Among diabetes antigen specific CD8+ T cells, T cell receptor and mTOR signaling were also reduced. Impairments in function of adaptive immune cells were enhanced by teplizumab treatment in EBV seropositive individuals. Our data indicate that EBV can impair signaling pathways in immune cells, that broadly redirect cell differentiation.
2025-05-15 | GSE296549 | GEO
Project description:Teplizumab is approved for delay of diagnosis of type 1 diabetes and modulates new onset disease. Compared to EBV seronegative patients, those who were EBV seropositive prior to treatment had a more robust response to drug in two clinical trials. We compared the phenotypes, transcriptomes, and development of peripheral blood cells before and after teplizumab treatment. Higher number of Tregs and “partially exhausted” CD8+ T cells were found in EBV seropositive individuals at the baseline in the TN10 and AbATE trials. Single cell transcriptomics and functional assays identified downregulation of NFB and other pathways after treatment in treated EBV seropositive patients. Among diabetes antigen specific CD8+ T cells, T cell receptor and mTOR signaling were also reduced. Impairments in function of adaptive immune cells were enhanced by teplizumab treatment in EBV seropositive individuals. Our data indicate that EBV can impair signaling pathways in immune cells, that broadly redirect cell differentiation.
2024-09-25 | GSE271063 | GEO
Project description:Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (single-cell RNA-seq of sorted CD8+ T-cells)
| PRJNA338798 | ENA
Project description:Teplizumab, a humanized anti-CD3 monoclonal antibody, represents a major advancement in autoimmune type 1 diabetes (T1D) treatment, capable of delaying clinical onset in stage 2 and preserving beta cell function in early stage 3. However, therapeutic responses are heterogeneous. To better understand this variability, we applied single-cell transcriptomics to paired peripheral blood and pancreas samples from anti-mouse CD3-treated non-obese diabetic (NOD) mice. This analysis identified distinct gene signatures associated with therapy success or resistance, with consistent patterns across both compartments. Success-associated signatures were enriched in NK/CD8⁺ T cells as well as other immune cell types, whereas resistance signatures were predominantly expressed by neutrophils. The immune communities underlying these response signatures were largely confirmed in human whole-blood sequencing data from the AbATE study at 6 months, which assessed teplizumab therapy in stage 3 T1D. Furthermore, baseline expression profiling in both the human TN10 (stage 2) and AbATE (stage 3) cohorts identified immune signatures predictive of therapy response, T cell-enriched signatures in responders and neutrophil-enriched signatures in non-responders, highlighting the critical roles of both adaptive and innate immunity in determining teplizumab outcome. Using an elastic-net logistic regression model, we developed a 26-gene blood-based signature capable of predicting teplizumab response with high accuracy (average AUC = 0.97 across bootstrapped datasets). Together, these findings demonstrate the predictive potential of immune gene signatures and highlight the value of transcriptomic profiling in guiding individualized treatment strategies with teplizumab in T1D.
2025-09-16 | GSE307823 | GEO
Project description:Lung CD8⁺ T cells induced during chronic tuberculosis exhibit functional heterogeneity, comprising both effector and exhausted states. CD226 is the most differentially expressed gene distinguishing effector from exhausted CD8⁺ T cells. Functionally, CD226 serves as a costimulatory molecule that promotes recognition of Mtb-infected macrophages. Loss of CD226 expression correlates with the onset of CD8⁺ T cell exhaustion during tuberculosis.
2025-07-22 | GSE302813 | GEO
Project description:CD8 T cells normally differentiate from resting naïve T cells into function effector and then memory CD8 T cells following acute infections. During chronic viral infections, however, virus-specific CD8 T cells often become exhausted. We used microarrays to examine the gene expression differences between naive, effector, memory and exhausted virus-specific CD8 T cells following lymphocytic choriomeningitis virus infection. Experiment Overall Design: Three or four independent samples were sorted by flow cytometry for each cell type (naive, effector, memory and exhausted) virus-specific CD8 T cells. RNA was extracted and hybridized to Affymetrix microarrays.
2008-06-16 | E-GEOD-9650 | biostudies-arrayexpress
Project description:B7x (B7-H4 or B7S1) is the seventh member of the B7 family and the in vivo function remains largely unknown. Despite new genetic data linking the B7x gene with autoimmune diseases, how exactly it contributes to peripheral tolerance and autoimmunity is unclear. Here we showed that B7x protein was not detected on antigen-presenting cells or T cells in both human and mice, which is unique in the B7 family. As B7x protein is expressed in some peripheral cells such as pancreatic b cells, we utilized a CD8 T cell-mediated diabetes model (AI4ab) in which CD8 T cells recognize an endogenous self-antigen, and found that mice lacking B7x developed more severe diabetes than control AI4ab mice. Conversely, mice overexpressing B7x in the b cells (Rip-B7xAI4ab) were diabetes free. Furthermore, adoptive transfer of effector AI4ab CD8 T cells induced diabetes in control mice, but not in Rip-B7xAI4ab mice. Mechanistic studies revealed that pathogenic effector CD8 T cells were capable of migrating to the pancreas but failed to robustly destroy tissue when encountering local B7x in Rip-B7xAI4ab mice. Although AI4ab CD8 T cells in Rip-B7xAI4ab mice and AI4ab mice showed similar cytotoxic function, cell death, and global gene expression profiles, these cells had greater proliferation in AI4ab mice than in RIP-B7xAI4ab mice. These results suggest that B7x in nonlymphoid organs prevents peripheral autoimmunity partially through inhibiting proliferation of tissue-specific CD8 T cells and that local overexpression of B7x on pancreatic b cells is sufficient to abolish CD8 T cell-induced diabetes. AI4 mice developed T1D and Rip-B7x AI4 mice were resistant to T1D. Total RNA was collected and gene expression compared between AI4 CD8 T cells from AI4 and Rip-B7xAI4 mice.
2012-08-21 | E-GEOD-40225 | biostudies-arrayexpress