Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA187929 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:CD4 T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for longlived antibody responses. However, it remains unclear whether there are CD4+ memory T cells committed to the Tfh lineage after antigen clearance. Using adoptive transfer of antigen-specific memory CD4+ subpopulations (based on CXCR5 and Ly6c expression)in the LCMV infection model, we found that there are distinct memory CD4+ T cell populations with commitment to the Tfh and Th1 lineages. Our conclusions are based on gene expression profiles, epigenetic studies and phenotypic and functional analysis. The gene expression profiles of virus-specific CD4 T cell subets at effector and memory stages is presented here. The SMARTA TCR transgenic / adptive transfer system was used to identify and sort subsets of antigen-specific CD4 T cells (based on their expression of Ly6c and CXCR5) elicited after acute infection with LCMV (Arm).
2013-04-22 | E-GEOD-43863 | biostudies-arrayexpress
Project description:TFH and Th1 cells generated after viral or intracellular bacterial infections are critical for the control of infections and the development of immunological memories. However, the mechanisms that govern the choice of activated CD4 T cells to the two alternative fates remain unclear. Here, we found that reciprocal expression of TCF1 and Blimp1 between viral-specific TFH and Th1 cells started early after infection. TCF1 was intrinsically required for the differentiation of TFH cells. In the absence of TCF1, TFH cells failed to maintain their transcriptional and metabolic signatures, distinct from those in Th1 cells. Mechanistically, TCF1 functioned through forming negative feedback loops with IL-2 and Blimp1 signaling. Thus, we have demonstrated an essential role of TCF1 in TFH-cell differentiation. Tcf7 deficient and WT SMARTA CD4 T cells were isolated from mice 8 days after Lymphocytic Choriomeningitis Virus (LCMV) infection. TFH and Th1 cells were separated by FACS.
2015-09-18 | E-GEOD-65660 | biostudies-arrayexpress
Project description:Following an infection, CD4+ lymphocytes can differentiate into long-lived memory T cells, some of which circulate through the secondary lymphoid organs (SLOs) while a population lodges in non-lymphoid tissues. While CD4+ T cells in SLOs have been examined, the developmental origins and transcriptional regulation of tissue-resident memory T cells (TRM) remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profile of virus-specific CD4+ TRM in the small intestine (SI) following acute lymphocytic choriomeningitis virus (LCMV) infection. LCMV-specific CD4+ TRM at day 7 of infection shared a gene-expression program and chromatin profile with TH1 cells and progressively acquired a mature TRM program by day 21 memory time point, supporting a developmental relationship between TRM and TH1 subsets. Furthermore, we demonstrated that TRM cells expressed genes associated with both effector and memory T cell fates, including the transcriptional regulators Blimp1, Id2, and Bcl6 which were necessary for CD4+ TRM differentiation. TH1-associated Blimp1 and Id2 were both required for early TRM formation, while TFH-associated Bcl6 initially inhibited TRM differentiation but was critical for development of long-lived TRM cells. Our results identify new significance for TFs previously associated with circulating CD4+ T cell populations and their roles in driving SI CD4+ TRM differentiation.
2023-06-30 | GSE184252 | GEO
Project description:Following an infection, CD4+ lymphocytes can differentiate into long-lived memory T cells, some of which circulate through the secondary lymphoid organs (SLOs) while a population lodges in non-lymphoid tissues. While CD4+ T cells in SLOs have been examined, the developmental origins and transcriptional regulation of tissue-resident memory T cells (TRM) remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profile of virus-specific CD4+ TRM in the small intestine (SI) following acute lymphocytic choriomeningitis virus (LCMV) infection. LCMV-specific CD4+ TRM at day 7 of infection shared a gene-expression program and chromatin profile with TH1 cells and progressively acquired a mature TRM program by day 21 memory time point, supporting a developmental relationship between TRM and TH1 subsets. Furthermore, we demonstrated that TRM cells expressed genes associated with both effector and memory T cell fates, including the transcriptional regulators Blimp1, Id2, and Bcl6 which were necessary for CD4+ TRM differentiation. TH1-associated Blimp1 and Id2 were both required for early TRM formation, while TFH-associated Bcl6 initially inhibited TRM differentiation but was critical for development of long-lived TRM cells. Our results identify new significance for TFs previously associated with circulating CD4+ T cell populations and their roles in driving SI CD4+ TRM differentiation.
2023-06-30 | GSE184262 | GEO
Project description:Following an infection, CD4+ lymphocytes can differentiate into long-lived memory T cells, some of which circulate through the secondary lymphoid organs (SLOs) while a population lodges in non-lymphoid tissues. While CD4+ T cells in SLOs have been examined, the developmental origins and transcriptional regulation of tissue-resident memory T cells (TRM) remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profile of virus-specific CD4+ TRM in the small intestine (SI) following acute lymphocytic choriomeningitis virus (LCMV) infection. LCMV-specific CD4+ TRM at day 7 of infection shared a gene-expression program and chromatin profile with TH1 cells and progressively acquired a mature TRM program by day 21 memory time point, supporting a developmental relationship between TRM and TH1 subsets. Furthermore, we demonstrated that TRM cells expressed genes associated with both effector and memory T cell fates, including the transcriptional regulators Blimp1, Id2, and Bcl6 which were necessary for CD4+ TRM differentiation. TH1-associated Blimp1 and Id2 were both required for early TRM formation, while TFH-associated Bcl6 initially inhibited TRM differentiation but was critical for development of long-lived TRM cells. Our results identify new significance for TFs previously associated with circulating CD4+ T cell populations and their roles in driving SI CD4+ TRM differentiation.
2023-06-30 | GSE184260 | GEO
Project description:Following an infection, CD4+ lymphocytes can differentiate into long-lived memory T cells, some of which circulate through the secondary lymphoid organs (SLOs) while a population lodges in non-lymphoid tissues. While CD4+ T cells in SLOs have been examined, the developmental origins and transcriptional regulation of tissue-resident memory T cells (TRM) remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profile of virus-specific CD4+ TRM in the small intestine (SI) following acute lymphocytic choriomeningitis virus (LCMV) infection. LCMV-specific CD4+ TRM at day 7 of infection shared a gene-expression program and chromatin profile with TH1 cells and progressively acquired a mature TRM program by day 21 memory time point, supporting a developmental relationship between TRM and TH1 subsets. Furthermore, we demonstrated that TRM cells expressed genes associated with both effector and memory T cell fates, including the transcriptional regulators Blimp1, Id2, and Bcl6 which were necessary for CD4+ TRM differentiation. TH1-associated Blimp1 and Id2 were both required for early TRM formation, while TFH-associated Bcl6 initially inhibited TRM differentiation but was critical for development of long-lived TRM cells. Our results identify new significance for TFs previously associated with circulating CD4+ T cell populations and their roles in driving SI CD4+ TRM differentiation.
2023-06-30 | GSE184259 | GEO
Project description:ATAC-Seq experiments were performed to elucidate the chromatin state changes among naïve CD4+ T cells, WT follicular helper T (TFH) cells and WT type 1 helper T (TH1) cells Day2 (D2), Day5 (D5), Day8 (D8) post-LCMV-Armstrong infection, as well as EZH2-null (KO) TFH and TH1 at Day8 post-LCMV-infection. The analysis suggested stringent lineage-specific mode of chromatin accessibility in each group, indicating chromatin remodeling is tightly associated with TFH versus TH1 lineage differentiation in response to acute viral infection. Furthermore, the comparison between wild-type and EZH2-null TFH cells showed that less-opening state of certain chromatin accessible region in TFH-differentiation associated genes in the formers, suggesting EZH2 led to permissive chromatin accessibility primarily at specific regions of TFH-associated genes. H3K27me3-ChIP-seq was performed in WT TFH and TH1 cells to confirm the deposition of the histone marks at those loci.
2018-12-31 | GSE120532 | GEO
Project description:CD4 T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for longlived antibody responses. However, it remains unclear whether there are CD4+ memory T cells committed to the Tfh lineage after antigen clearance. Using adoptive transfer of antigen-specific memory CD4+ subpopulations (based on CXCR5 and Ly6c expression)in the LCMV infection model, we found that there are distinct memory CD4+ T cell populations with commitment to the Tfh and Th1 lineages. Our conclusions are based on gene expression profiles, epigenetic studies and phenotypic and functional analysis. The gene expression profiles of virus-specific CD4 T cell subets at effector and memory stages is presented here.
2013-04-22 | GSE43863 | GEO
Project description:Humoral and cellular immunity upon viral infections usually co-exist; however, sometimes, one of the two responses emerges as dominant and is responsible for most of the antiviral activity. For example, infection with lymphocytic choriomeningitis virus (LCMV) induces very strong cellular responses, but weak and inefficient neutralizing Ab (nAb) responses. Lack of nAb responses is an important issue for complete clearance of LCMV and other similar viruses, which in some instances tend to establish chronic infections. Recent work from our group has shown that this unbalance is observed also at the level of CD4 T cells responses, with subcutaneous LCMV infection leading almost exclusively to TH1 but no TFH differentiation. Here, we report that LCMV-induced TH1 cells are heterogeneous and comprise a Tcf-1+ subset and a GzmB+ subset. We found that none of the subsets is dependent on the major TH1-polarizing cytokine IL-12. Instead, IFN-gamma (IFN-g) was found to promote the development of GzmB+ cells and to suppress the commitment of the Tcf-1+ population into fully differentiated TFH. As a result, blockade of IFN-g led to a rescue in the TFH population, germinal center B cells and antibody responses. Our results shed light on new mechanisms underlying the inefficient nAbs production in response to non-cytopathic viruses such as LCMV and are promising for the design of new vaccination strategies.
2025-03-25 | GSE250209 | GEO
Project description:Humoral and cellular immunity upon viral infections usually co-exist; however, sometimes, one of the two responses emerges as dominant and is responsible for most of the antiviral activity. For example, infection with lymphocytic choriomeningitis virus (LCMV) induces very strong cellular responses, but weak and inefficient neutralizing Ab (nAb) responses. Lack of nAb responses is an important issue for complete clearance of LCMV and other similar viruses, which in some instances tend to establish chronic infections. Recent work from our group has shown that this unbalance is observed also at the level of CD4 T cells responses, with subcutaneous LCMV infection leading almost exclusively to TH1 but no TFH differentiation. Here, we report that LCMV-induced TH1 cells are heterogeneous and comprise a Tcf-1+ subset and a GzmB+ subset. We found that none of the subsets is dependent on the major TH1-polarizing cytokine IL-12. Instead, IFN-gamma (IFN-g) was found to promote the development of GzmB+ cells and to suppress the commitment of the Tcf-1+ population into fully differentiated TFH. As a result, blockade of IFN-g led to a rescue in the TFH population, germinal center B cells and antibody responses. Our results shed light on new mechanisms underlying the inefficient nAbs production in response to non-cytopathic viruses such as LCMV and are promising for the design of new vaccination strategies.
2025-03-25 | GSE239968 | GEO