Gene expression of CD4+CD8+ Tfh cells and CD4+CD8- Tfh in tonsil.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE202616 | GEO | 2022/08/10
REPOSITORIES: GEO
Similar Datasets
Project description:To further know features of CD4+CD8+ Double positive (DP)-Tfh cells in respective lymphoid tissues, we subsequently investigated transcriptomes of DP-Tfh cells in submandibular gland lesions of IgG4-RD in comparison to those of DP-Tfh cells in tonsils. Results showed that DP-Tfh cells of IgG4-RD lesions were more apt to present CTL-related genes such as Eomes and granzymes than DP-Tfh cells in tonsils. It was also noted that the level of CD70 in DP-Tfh cells of IgG4-RD lesions was higher than that of tonsillar DP-Tfh cells. Genes related to Tfh cell function were seemed to be presented in DP-Tfh cells of tonsils compared to DP-Tfh cells of IgG4-RD lesions.
2022-08-10 | GSE202617 | GEO
Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation. Analysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) WT and Sh2d1a-/- follicular helper CD4 T cells (CXCR5high),versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection.
2010-04-28 | E-GEOD-21379 | biostudies-arrayexpress
Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation. Analysis of in vivo polyclonal GC Tfh vs Tfh vs Non-Tfh eight days after LCMV viral infection. Analysis of in vivo follicular helper CD4 T cells (CXCR5high GL7low), versus germinal center follicular helper CD4 T cells (CXCR5hi GL7hi), versus non-follicular helper CD4 T cells (CXCR5low) eight days after viral infection.
2010-04-28 | E-GEOD-21380 | biostudies-arrayexpress
Project description:After activation, CD4+ helper T (Th) cells differentiate; into distinct effector subsets. Although chemokine; (C-X-C motif) receptor 5-expressing T follicular; helper (Tfh) cells are important in humoral immunity,; their developmental regulation is unclear. Here we; show that Tfh cells had a distinct gene expression; profile and developed in vivo independently of the; Th1 or Th2 cell lineages. Tfh cell generation was regulated; by ICOS ligand (ICOSL) expressed on B cells; and was dependent on interleukin-21 (IL-21), IL-6,; and signal transducer and activator of transcription; 3. However, unlike Th17 cells, differentiation of Tfh; cells did not require transforming growth factor; b (TGF-b) or Th17-specific orphan nuclear receptors; RORa and RORg in vivo. Finally, naive T cells activated; in vitro in the presence of IL-21 but not; TGF-b signaling preferentially acquired Tfh gene; expression and promoted germinal-center reactions; in vivo. This study thus demonstrates that Tfh is a; distinct Th cell lineage. Experiment Overall Design: Splenic CD4+CXCR5+ T cells were isolated from KLH-immunized mice and restimulated with anti-CD3 for 4 hours before total RNA preparation. Affymetrix gene chips were used to analyze their gene expression.
2008-10-21 | E-GEOD-11924 | biostudies-arrayexpress
Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation.
2010-04-20 | GSE21379 | GEO
Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation.
2010-04-20 | GSE21380 | GEO
Project description:According to the WHO 2009 classification, dengue with warning signs (D+W) is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which is a serious complication associated with higher morbidity and mortality. We report that the frequency of CD4+CD8+ double-positive (DP) T cells is significantly increased in patients at risk of developing plasma leakage. Transcriptomic analysis demonstrated that CD4+CD8+ DP cells were distinct from CD4+ Single Positive (SP) T cells, but co-clustered with CD8+ SP cells indicating a largely similar transcriptional profile. 20 significant differentially expressed (DE) genes were identified between CD4+CD8+ DP and CD8+ SP cells. These genes encode OX40 and CCR4 (TNFRSF4 and CCR4), as well as other molecules associated with cell signaling on the cell surface (NT5E, MXRA8, PTPRK). While 5 significant DE genes were identified, the profile of gene expression in CD4+CD8+ DP cells was mostly similar between patients with and without warning signs of plasma leakage, implying a role of CD4+CD8+ DP cells in plasma leakage through a quantitative increase rather than functional alteration. The differentially expressed genes identified could have diagnostic utility, perhaps as PCR-based diagnostic markers.
2021-06-16 | GSE178240 | GEO
Project description:The production of IL-21 by T follicular helper (Tfh) cells is vital in driving the germinal centre reaction and high affinity antibody formation. However, the degree of Tfh cell heterogeneity and function is not fully understood. Using a novel IL-21eGFP reporter mouse strain, we identified a subpopulation of GFP+ highly differentiated Tfh cells in Peyer’s Patches. In vitro, GFP+ cells that did not co-express IL-17 or Foxp3 were induced by CD3 and CD28 stimulation of naïve CD4+ cells from IL-21eGFP mice in cultures containing IL-6, TGFβ and retinoic acid. In vivo, the differentiation of GFP+Tfh cells in Peyer’s Patches was induced by intestinal bacteria, and required CD4+ T cells and B cells with diverse repertoires. Analysis of the TCRβ repertoire of Peyer’s Patches CD4+ T cell subpopulations demonstrated that GFP+Tfh cells are polyclonal and closely related to GFP-Tfh cells. Importantly, ablation of GFP+ cells resulted in a reduced frequency of Peyer’s Patches germinal center B cells and small but significant shifts in gut microbiome composition. Thus, using a new IL-21-reporter mouse we have identified a subpopulation of Tfh cells induced by the gut microbiota and necessary for optimal Peyer’s Patches germinal center responses.
2018-01-01 | GSE77899 | GEO
Project description:During chronic viral infection, the inflammatory function of CD4 T cells becomes gradually attenuated. Concurrently, Th1 cells progressively acquire the capacity to secrete the cytokine IL-10, a potent suppressor of antiviral T cell responses. To determine the transcriptional changes that underlie this T cell adaption process, we applied a single-cell RNA-sequencing approach and assessed the heterogeneity of IL-10-expressing CD4 T cells during chronic infection. Unexpectedly, our analyses revealed an IL-10-producing population with a robust Tfh-signature. Using IL-10 and IL-21 double-reporter mice, we further demonstrate that IL-10+IL-21+co-producing Tfh cells arise predominantly during chronic but not acute LCMV infection. Importantly, depletion of IL-10+IL-21+co-producing CD4 T cells or deletion of Il10 specifically in Tfh cells resulted in impaired humoral immunity and viral control. Mechanistically, B cell-intrinsic IL-10 signaling was required for sustaining germinal center reactions. Lastly, we demonstrate that IL-27 and type I IFNs differentially regulate the formation of this protective IL-10-producing Tfh subset. Thus, our findings elucidate a critical role for Tfh-derived IL-10 in promoting humoral immunity during persistent viral infection.
2018-10-29 | GSE111025 | GEO
Project description:Effective immunity to viruses such as influenza and SARS-CoV-2 requires the generation of CD4+ T cell subsets that coordinate complementary aspects of the immune response. These include T follicular helper (TFH) and T helper 1 (TH1) cells, which promote humoral and cell-mediated helper responses, respectively. A third population, CD4+ cytotoxic T lymphocytes (CD4-CTLs) facilitates clearance of infection via mechanisms normally associated with CD8+ T cells, including perforin-mediated destruction of infected cells. Here, we identify the transcription factor Aiolos as a reciprocal regulator of TFH and CD4-CTL responses. We demonstrate that Aiolos deficiency compromises TFH differentiation and antibody production during influenza infection. Conversely, we find that CD4+ T cells acquire a cytotoxic-like program in the absence of Aiolos, including increased expression of the CTL-associated transcription factors Eomes and Blimp-1. We further show that while Aiolos positively regulates the TFH transcriptional regulators Zfp831, Tcf-1 and Bcl-6, it also directly represses expression of IL-2Ra and IL-2/STAT5-driven expression of the cytotoxic gene program. Thus, our findings identify Aiolos as a pivotal regulator of TFH and CD4-CTL differentiation and highlight its potential as a therapeutic target for the manipulation of CD4+ T cell humoral and cytotoxic responses.
2023-02-01 | GSE203064 | GEO