Murine cytotoxic CD4 T cells
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ABSTRACT:
PROVIDER: PRJNA743066 | ENA |
REPOSITORIES: ENA
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Project description:Cytotoxic CD4 T lymphocytes (CD4-CTL) are important in anti-viral immunity. For example, we have previously shown that in mice, CD4-CTL are important to control ectromelia virus (ECTV) infection. How viral infections induce CD4-CTL responses remains incompletely understood. Here we demonstrate that not only ECTV but also vaccinia virus and Lymphocytic Choriomeningitis virus induce CD4-CTL, but that the response to ECTV is stronger. Using ECTV, we also demonstrate that in contrast to CD8-CTL, CD4-CTL differentiation requires constant virus replication and ceases once the virus is controlled. We also show that Major Histocompatibility Complex Class II molecules on CD11c+ cells are required for CD4-CTL differentiation and for mousepox resistance. Transcriptional analysis indicated that anti-viral CD4-CTL and non-cytolytic T Helper 1 (Th1) CD4 T cells have similar transcriptional profiles, suggesting that CD4-CTL are terminally differentiated classical Th1 cells. Interestingly, CD4-CTL and classical Th1 cells expressed similar mRNA levels of the transcription factors ThPOK and GATA-3, necessary for CD4 T cell linage commitment; and Runx3, required for CD8 T cell development and effector function. However, at the protein level, CD4-CTL had higher levels of the three transcription factors suggesting that further post-transcriptional regulation is required for CD4-CTL differentiation. Finally, using CRISPR-Cas9 deletion of Runx3 in CD4 T cells, we demonstrate that the development of CD4-CTL but not of classical Th1 CD4 T cells requires Runx3 following ECTV infection. These results further our understanding of the mechanisms of CD4-CTL differentiation during viral infection and the role of post-transcriptionally regulated Runx3 in this process.
2021-07-06 | GSE179289 | GEO
Project description:We compared gene expression profiling between CD4+ helper T cells and CD8+ cytotoxic T cells CD4+ helper T cells vs CD8+ cytotoxic T cells
2015-06-30 | E-GEOD-67204 | biostudies-arrayexpress
Project description:The methylation profile of human cytotoxic CD4 T cells was compared to their naive counterpart, to central memory Th1 cells, and to naive and cytotoxic CD8 T cells in order to elucidate the epigenetic basis of cytotoxic differentiation in CD4 T cells.
2018-03-06 | GSE75405 | GEO
Project description:The transcriptional profile of human cytotoxic CD4 T cells was compared to their naive counterpart, to central memory Th1 cells, and to naive and cytotoxic CD8 T cells in order to elucidate the epigenetic basis of cytotoxic differentiation in CD4 T cells.
2018-03-06 | GSE75404 | GEO
Project description:Most people infected by EBV acquire specific immunity, which then controls latent infection throughout their life. Immune surveillance of EBV-infected cells by cytotoxic CD4+ T cells has been recognized; however, the molecular mechanism of generating cytotoxic effector T cells of the CD4+ subset remains poorly understood. Here we compared phenotypic features and the transcriptome of EBV-specific effector-memory CD4+ T cells and CD8+ T cells in mice and found that both T cell types show cytotoxicity and, to our surprise, widely similar gene expression patterns relating to cytotoxicity. Similar to cytotoxic CD8+ T cells, EBV-specific cytotoxic CD4+ T cells from human peripheral blood expressed T-bet, Granzyme B, and Perforin and upregulated the degranulation marker, CD107a, immediately after restimulation. Furthermore, T-bet expression in cytotoxic CD4+ T cells was highly correlated with Granzyme B and Perforin expression at the protein level. Thus, differentiation of EBV-specific cyto toxic CD4+ T cells is possibly controlled by mechanisms shared by cytotoxic CD8+ T cells. T-bet-mediated transcriptional regulation may explain the similarity of cytotoxic effector differentiation between CD4+ T cells and CD8+ T cells, implicating that this differentiation pathway may be directed by environmental input rather than T cell subset.
2022-08-26 | GSE206802 | GEO
Project description:We compared gene expression profiling between CD4+ helper T cells and CD8+ cytotoxic T cells
2015-06-30 | GSE67204 | GEO
Project description:The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present a large-scale single-cell transcriptomic analysis of viral antigen-reactive CD4+ T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, we found increased proportions of cytotoxic follicular helper (TFH) cells and cytotoxic T helper cells (CD4-CTLs) responding to SARS-CoV-2, and reduced proportion of SARS-CoV-2-reactive regulatory T cells (TREG). Importantly, in hospitalized COVID-19 patients, a strong cytotoxic TFH response was observed early in the illness which correlated negatively with antibody levels to SARS-CoV-2 spike protein. Polyfunctional T helper (TH)1 and TH17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4+ T cells compared to influenza-reactive CD4+ T cells. Together, our analyses provide so far unprecedented insights into the gene expression patterns of SARS-CoV-2-reactive CD4+ T cells in distinct disease severities.
2020-10-06 | GSE152522 | GEO
Project description:In addition to helper and regulatory potential, CD4+T cells also acquire cytotoxic activity marked by granzyme B (GzmB) expression and the ability to promote rejection of established tumors. Here we examined the molecular and cellular mechanisms underpinning the differentiation of cytotoxic CD4+T cells following immunotherapy. CD4 transfer into lymphodepleted animals or regulatory T cell (Treg)depletion promoted GzmB expression by tumor-infiltrating CD4+which was prevented by IL-2 neutralization. Transcriptional analysis revealed a polyfunctional helper and cytotoxic phenotype characterized bythe expression of the transcription factors T-bet and Blimp-1. Whilst T-bet ablation restrictedIFN-gproduction, lossof Blimp-1preventedGzmB expressionin response to IL-2, suggesting these are two independent programs required forpolyfunctionality of tumor-reactive CD4+T cells. The data underscores the role of Treg, IL-2 and Blimp-1 controlling the differentiation of cytotoxic T cells and offers a pathway to enhancement of anti-tumor activity through their manipulation.
2019-12-18 | GSE141540 | GEO
Project description:Rheumatoid arthritis is an autoimmune disease affecting the synovial joints where CD4+ T cells play a pathogenic role. However, a deeper analysis of cytotoxic CD4+ T cells is still lacking, particularly in the context of the recently described peripheral helper T-cell subset (TPH). Here, we show, using 10X-single-cell sequencing and multi-parameter flow cytometry that cytotoxic CD4+ T cells are enriched in synovial fluid (SF) of anti-citrullinated peptides antibody (ACPA)-positive RA patients. We also identify two distinct TPH clusters differentially characterized by the expression of CXCL13 and PRDM1, respectively. Our data reveal that the adhesion G-Protein Coupled Receptor 56 (GPR56), a marker of circulating cytotoxic cells, delineates the TPH CD4+ T-cell subset in SF. At the site of inflammation, GPR56+ CD4+ T cells expressed the tissue-resident memory markers LAG-3, CXCR6, and CD69. Further, TCR clonality analysis revealed that most of the expanded clones in PB and SF are contained within the cytotoxic CD4+ T-cell population. Finally, the detection of common TCRs between the two TPH and cytotoxic CD4+ T cell clusters suggests a common differentiation pathway between these three subsets. Our study provides a better overview of the different pathogenic T-cell subsets at the site of inflammation in ACPA+ RA and suggests GPR56 as a therapeutic target to modulate TPH cells and cytotoxic CD4+ T cell function.
| EGAS00001005241 | EGA
Project description:We show here that the T helper-fate is not fixed and that mature antigen-stimulated CD4 T cells can switch off Thpok expression and reactivate CD8- lineage genes. This unexpected plasticity results in the post-thymic termination of the T helper- program and the functional differentiation of distinct MHC class II restricted CD4 cytotoxic T lymphocytes Small intestine CD4 intraepithelial T lymphocytes from ThPOK-GFP reposter mice were isolated and sorted (FACS Aria) based on ThPOK and CD8aa expression. Cell were isolated either from non-experimental ThPOK-GFP reporter mice (WT) or after transfering CD4 naive T cells from ThPOK-GFP reporter mice to RAG-/-recipient animals (TR) as an experimental colitis model. Experimet was done in duplicate.
2012-12-10 | E-GEOD-42277 | biostudies-arrayexpress