RNA-seq analysis of functionally distinct HLADR+CD38+ CD8 T cells from acute dengue febrile patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE212034 | GEO | 2023/09/22
REPOSITORIES: GEO
Similar Datasets
Project description:RNA-seq analysis of functionally distinct HLADR+CD38+ CD8 T cells from acute dengue febrile patients
| PRJNA873677 | ENA
Project description:CD38 and CD49d are associated negative prognosticators in chronic lymphocytic leukemia (CLL). Despite evidence that both molecules are involved in interactions occurring between CLL and normal cells in the context of CLL-involved tissues, a functional link is still missing. Using gene expression profiles comparing CD38+CD49d+ vs. CD38-CD49d- CLL cells, we demonstrated overexpression of the CCL3 and CCL4 chemokines in cells from the former group. These chemokines were also upregulated by CD38 signals in CLL; moreover, CCL3 was expressed by CLL cells from bone marrow biopsies (BMB) of CD38+CD49d+ but not CD38-CD49d- cases. High levels of CCR1 and, to a lesser extent, CCR5, the receptors for CCL3 and CCL4, were found in CLL-derived monocyte-macrophages. Consistently, CCL3 increased monocyte migration, and CD68+ macrophage infiltration was particularly high in BMB from CD38+CD49d+ CLL. Conditioned media from CCL3-stimulated macrophages induced endothelial cells to express VCAM-1, the CD49d ligand, likely through TNFα over-production. These effects were apparent in BMB from CD38+CD49d+CLL, where lymphoid infiltrates were characterized by a prominent meshwork of VCAM-1+ stromal/endothelial cells. Lastly, CD49d engagement by VCAM-1-transfectants increased viability of CD38+CD49d+ CLL cells. Altogether, CD38 and CD49d can be thought of as a part of a consecutive chain of events ultimately leading to improved survival of CLL cells.
2009-03-03 | GSE14560 | GEO
Project description:PD-1 blockade therapy, harnessing the cytotoxic potential of CD8+ T cells, has yielded clinical success in treating malignancies. However, its efficacy is often limited due to the progressive differentiation of intratumoral CD8+ T cells into a hypofunctional state known as terminal exhaustion. Despite identifying CD8+ T cell subsets associated with immunotherapy resistance, the molecular pathway triggering the resistance remains elusive. Given the clear association of CD38 with CD8+ T cell subsets resistant to anti-PD1 therapy, we investigated its role in inducing resistance. Phenotypic and functional characterization, along with single-cell RNA sequencing analysis of both in vitro chronically stimulated and intratumoral CD8+ T cells, revealed that CD38-expressing CD8+ T cells are terminally exhausted. Exploring the molecular mechanism, we discovered that CD38 expression was crucial in promoting terminal differentiation of CD8+ T cells by suppressing TCF1 expression, thereby rendering them unresponsive to anti-PD1 therapy. Genetic ablation of CD38 in tumor reactive CD8+ T cells restored TCF1 levels and improved the responsiveness to anti-PD1 therapy in mice. Mechanistically, CD38 expression on exhausted CD8+ T cells elevated intracellular Ca2+ levels through RyR2 calcium channel activation. This, in turn, promoted chronic AKT activation, leading to TCF1 loss. Knockdown of RyR2 or inhibition of AKT in CD8+ T cells maintained TCF1 levels, induced a sustained anti-tumor response, and enhanced responsiveness to anti-PD1 therapy. Thus, targeting CD38 represents a potential strategy to improve the efficacy of anti-PD1 treatment in cancer.
2024-01-12 | GSE251829 | GEO
Project description:Treatment resistance of leukemia stem cells (LSCs) and suppression of the autologous immune system represent major challenges to achieve a cure in acute myeloid leukemia (AML). Although AML blasts generally retain high levels of surface CD38 (CD38pos), LSCs are frequently enriched in the CD34posCD38neg blast fraction. Here, we report that IFNγ reduces LSCs clonogenic activity and induces CD38 upregulation in both CD38pos and CD38neg LSC-enriched blasts. IFNγ-induced CD38 upregulation depends on IRF-1 transcriptional activation of the CD38 promoter. To leverage this observation, we created a novel compact, single-chain CD38-CD3 T cell engager (BN-CD38) designed to promote an effective immunological synapse between both CD8 and CD4 T cells and CD38pos AML cells. We demonstrate that BN-CD38 engages autologous CD4pos and CD8pos T cells and CD38pos AML blasts leading to T cell activation and expansion and to the elimination of leukemia cells in an autologous setting. Importantly, BN-CD38 engagement induces the release of high levels of IFNγ, driving the expression of CD38 on CD34posCD38neg LSC-enriched blasts and their subsequent elimination. Critically, while BN-CD38 showed significant in vivo efficacy across multiple disseminated AML cell lines and patient derived xenograft models, it did not affect normal hematopoietic stem cell clonogenicity and the development of multi-lineage human immune cells in CD34pos humanized mice. Taken together, this study provides important insights to target and eliminate AML LSCs.
2024-01-27 | GSE253921 | GEO
Project description:Treatment resistance of leukemia stem cells (LSCs) and suppression of the autologous immune system represent major challenges to achieve a cure in acute myeloid leukemia (AML). Although AML blasts generally retain high levels of surface CD38 (CD38pos), LSCs are frequently enriched in the CD34posCD38neg blast fraction. Here, we report that IFNγ reduces LSCs clonogenic activity and induces CD38 upregulation in both CD38pos and CD38neg LSC-enriched blasts. IFNγ-induced CD38 upregulation depends on IRF-1 transcriptional activation of the CD38 promoter. To leverage this observation, we created a novel compact, single-chain CD38-CD3 T cell engager (BN-CD38) designed to promote an effective immunological synapse between both CD8 and CD4 T cells and CD38pos AML cells. We demonstrate that BN-CD38 engages autologous CD4pos and CD8pos T cells and CD38pos AML blasts leading to T cell activation and expansion and to the elimination of leukemia cells in an autologous setting. Importantly, BN-CD38 engagement induces the release of high levels of IFNγ, driving the expression of CD38 on CD34posCD38neg LSC-enriched blasts and their subsequent elimination. Critically, while BN-CD38 showed significant in vivo efficacy across multiple disseminated AML cell lines and patient derived xenograft models, it did not affect normal hematopoietic stem cell clonogenicity and the development of multi-lineage human immune cells in CD34pos humanized mice. Taken together, this study provides important insights to target and eliminate AML LSCs.
2024-01-27 | GSE253920 | GEO
Project description:CD38 expression is an important prognostic marker in CLL with high levels of CD38 associated with shorter overall survival. In this study, we used gene expression profiling and protein analysis of highly purified cell-sorted CD38+ and CD38- chronic lymphocytic leukemia cells to elucidate a molecular basis for the association between CD38 expression and inferior clinical outcome. Paired CD38+ and CD38- CLL cells derived from the same patient were shown to be monoclonal by VH gene sequencing but despite this, CD38+ CLL cells possessed a distinct gene expression profile when compared with their CD38- sub-clones. Keywords: Sub-clonal analysis of CLL cells derived from the same leukemia sample
2006-11-23 | GSE6321 | GEO
Project description:B-cell chronic lymphocytic leukemia (B-CLL) is a heterogenous disease with a highly variable clinical course and analysis of ZAP-70 and CD38 expression on B-CLL cells allowed for identification of patients with good (ZAP-70-CD38-), intermediate (discordant expression of ZAP-70 and CD38) and poor (ZAP-70+CD38+) prognosis. In an attempt to identify a molecular basis that may underly this diverse clinical behaviour DNA microarray technology was employed to compare eight ZAP-70+CD38+ with eight ZAP-70-CD38- B-CLL cases. We used microarrays to detail the global programme of gene expression distinguising B-CLL from patient with good (samples 1 to 8) and poor prognosis (sample 9 to 16) and identified distinct classes of up- and down-regulated genes. Keywords: Disease progression
2006-09-22 | GSE4392 | GEO
Project description:Severe COVID-19 is characterized by a cytokine-mediated acute respiratory distress syndrome resembling toxic shock syndrome. We identified a SARS-CoV-2 S1 spike peptide (P3) with sequence homology to bacterial super-antigens. Computational modelling revealed P3 binding to MHC class I/II and TCR regions that partially overlap with staphylococcal enterotoxin B (SEB) and enterotoxin H (SEH) binding sites. In vitro, P3 potently activated 25-40% of human CD4 and CD8 T cells, accompanied by the increased expression of effector molecules IFNg and granzyme B. In vivo, P3 peptide administration to mice induced an inflammatory response characterized by elevated levels of proinflammatory cytokines, IL1b, IL6 and TNFa. Further, the P3 peptide promoted a more robust in vitro immune response of T-cells from COVID-19 patients with severe disease, as evidenced by increased CD69 and IFNg expression. Consistent with its super-antigenic properties, P3 preferentially also expanded T cells bearing restricted TCR Vα and Vβ chain repertoires in vitro. Overall, the homology of the P3 peptide to several endogenous mammalian proteins suggests the potential for the future discovery of related peptides that may contribute to inflammation and autoimmune disorders in humans.
2024-11-12 | GSE281135 | GEO
Project description:Upon antigen encounter, T cells can rapidly divide and form short-lived effector cells which plays an important role fighting an active infection. However, little is known about the molecular markers that distinguish such effector cells from other T cell populations in humans. Due to previous exposure with Mycobacterium tuberculosis (Mtb), we expect latent tuberculosis infected (LTBI) subjects to have Mtb-specific memory CD4 T cells that are capable of rapid expansion upon antigen re-encounter. To investigate this further we designed an in vitro MTP-AE (Memory T cell Proliferation upon Antigen Exposure) assay to track and isolate proliferated CD4 T cells in response to antigen stimulation. PBMCs from LTBI subjects were cultured with the MTB300 (Mtb specific peptide pool, PMID: 27409590) for 8 days before sorting for HLADR+ vs HLADR- and divided vs undivided CD4 T cells. We found that HLADR is a marker of recently divided memory CD4 T cells and that differentially expessed genes in HLADR+/recently divided cells were enriched for cytotoxic markers and cytokines compared to HLADR-/undivided cells.
2021-05-11 | GSE162725 | GEO
Project description:Gene expression profiles of CD34+CD38- stem cells and more differentiated CD34+CD38+ progenitor cells were compared. Comparison of expression profiles of hematopoietic stem cells from fetal liver, umbilical cord blood, bone marrow and mobilized pheripheral blood allowed us to identify a unique set of genes with conserved expression during ontogeny. Experiment Overall Design: CD34+CD38- en CD34+CD38+ cell populations were isolated by cell sorting from human Bone Marrow, mobilized peripheral blood, umbilical cord blood and fetal liver. Total RNA was isolated from each cell population followed by the synthesis of biotinylated cRNA. After fragmentation the biotinylated cRNA was hybridized to affymetrix U133A chips.
2008-10-25 | E-GEOD-6146 | biostudies-arrayexpress