Macaca mulatta
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA321418 | ENA |
REPOSITORIES: ENA
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Project description:A range of current candidate AIDS vaccine regimens are focused on generating protective HIV neutralizing antibody responses. Many of these efforts rely on the rhesus macaque animal model. Understanding how protective antibody responses develop and how to increase their efficacy are both major knowledge gaps. Germinal centers (GC) are the engines of antibody affinity maturation. GC T follicular helper (GC Tfh) CD4 T cells are required for GCs. Studying vaccine-specific GC Tfh cells after protein immunizations has been challenging, as antigen-specific GC Tfh cells are difficult to identify by conventional intracellular cytokine staining (ICS). Cytokine production by GC Tfh cells may be intrinsically limited in comparison to other T helper effector cells, as the biological role of a GC Tfh cell is to provide help to individual B cells within the GC, rather than secreting large amounts of cytokines bathing a tissue. To test this idea, we developed a cytokine-independent method to identify antigen-specific GC Tfh cells. RNAseq was performed using TCR stimulated GC Tfh cells to identify candidate markers based on differentially expressed genes and other criteria. Validation experiments determined CD25 (IL2Ra) and OX40 to be highly upregulated activation induced markers on the surface of GC Tfh cells after stimulation. In comparison to ICS, the activation induced marker (AIM) assay identified > 10-fold more antigen-specific GC Tfh cells in HIV Env protein immunized macaques (BG505 SOSIP). Additionally, the AIM assay detected antigen-specific CXCR5+ and CXCR5- CD4 T cells in peripheral blood. Thus, AIM demonstrates that antigen-specific GC Tfh cells are intrinsically stingy producers of cytokines, which is likely an essential part of their biological function. Total RNA obtained from GC Tfh cells from 3 rhesus macaque lymph node cell samples stimulated with Staphylococcal Enterotoxin B compared with 2 unstimulated cell samples.
2016-09-07 | E-GEOD-81382 | biostudies-arrayexpress
Project description:A range of current candidate AIDS vaccine regimens are focused on generating protective HIV neutralizing antibody responses. Many of these efforts rely on the rhesus macaque animal model. Understanding how protective antibody responses develop and how to increase their efficacy are both major knowledge gaps. Germinal centers (GC) are the engines of antibody affinity maturation. GC T follicular helper (GC Tfh) CD4 T cells are required for GCs. Studying vaccine-specific GC Tfh cells after protein immunizations has been challenging, as antigen-specific GC Tfh cells are difficult to identify by conventional intracellular cytokine staining (ICS). Cytokine production by GC Tfh cells may be intrinsically limited in comparison to other T helper effector cells, as the biological role of a GC Tfh cell is to provide help to individual B cells within the GC, rather than secreting large amounts of cytokines bathing a tissue. To test this idea, we developed a cytokine-independent method to identify antigen-specific GC Tfh cells. RNAseq was performed using TCR stimulated GC Tfh cells to identify candidate markers based on differentially expressed genes and other criteria. Validation experiments determined CD25 (IL2Ra) and OX40 to be highly upregulated activation induced markers on the surface of GC Tfh cells after stimulation. In comparison to ICS, the activation induced marker (AIM) assay identified > 10-fold more antigen-specific GC Tfh cells in HIV Env protein immunized macaques (BG505 SOSIP). Additionally, the AIM assay detected antigen-specific CXCR5+ and CXCR5- CD4 T cells in peripheral blood. Thus, AIM demonstrates that antigen-specific GC Tfh cells are intrinsically stingy producers of cytokines, which is likely an essential part of their biological function.
2016-09-07 | GSE81382 | GEO
Project description:Follicular helper T (Tfh) are a subset of CD4+ T helper cells that provide help to germinal center B cells and mediate the development of long-lived humoral immunity. Tfh cells dysregulation is associated with several major autoimmune diseases. Although recent studies showed Tfh cells differentiation is controlled by the transcription factor Bcl6, cytokines and cell-cell signals, limited information is available on the proteome and post-translational modifications (PTM) of proteins in human Tfh cells. In this study, using TMT labeling technique, antibody-based affinity enrichment and high-resolution LC-MS/MS analysis, we investigated quantitative proteome and acetylome in human naive CD4+ T cells and in vitro induced Tfh (iTfh) cells. In total, we identified 802 up-regulated proteins and 598 down-regulated proteins at the threshold of 1.5 folds in iTfh cells compared to naive CD4+ T cells. With the aid of intensive bioinformatics, biological process, cellular compartment, molecular function, KEGG pathway and protein-protein interaction of these differentially expressed proteins were revealed. Moreover, our acetylome data showed that 22 lysine acetylated proteins are up-regulated and 26 lysine acetylated proteins are down-regulated in iTfh cells compared to the naive CD4+ T cells, among which 11 differentially acetylated lysine residues in core histone were identified, indicating proteins acetylation and epigenetic mechanism are involved in regulating Tfh cells differentiation. These data provide a significant resource for studies of Tfh differentiation and normal and perturbed Tfh cell function.
2021-03-19 | PXD008563 | Pride
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:Generation of Tier 2 HIV neutralizing antibody (nAb) responses by immunization remains a challenging problem, and the immunological barriers to induction of such responses by Env immunogens remain unclear. We explored these barriers by combining a suite of innovative techniques, including longitudinal lymph node fine needle aspirates, germinal center (GC) B cell lineage tracking, and a new method for detecting and quantifying GC T follicular helper (GC Tfh) cells, in non-human primates immunized with a native-like HIV-1 Env trimer protein (BG505 SOSIP.v5.2). A majority of immunized animals (9/12) developed Tier 2 neutralizing antibodies (nAb). Tier 2 nAb development best correlated with GC B cell magnitude in response to later booster immunizations and the quality of the Tfh help. Notably, these immunological factors distinguished between qualitatively successful and unsuccessful vaccine Ab responses, as they correlated with nAb development but did not correlate with simple Env Ab binding titers. Therefore, direct probing of germinal centers in future vaccine trials is key, as this suite of technically robust approaches provides quantitation of the proximal immune correlates of neutralizing antibody development and could allow redesign of optimal multi-stage vaccination schedules.
2016-12-31 | GSE89148 | GEO
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:Follicular helper T (Tfh) cells access the B cell follicle to promote antibody responses, and are particularly important for germinal center (GC) reactions. However, the molecular mechanisms of how Tfh cells are physically associated with GCs are incompletely understood. Here we report that the sphingosine-1-phosphate receptor 2 (S1PR2) gene is highly expressed in a subpopulation of Tfh cells that localizes in GCs. S1PR2-deficient Tfh cells exhibited reduced accumulation in GCs due to their impaired retention. T cells deficient in both S1PR2 and CXCR5 were ineffective in supporting GC responses compared to T cells deficient only in CXCR5. These results suggest that S1PR2 and CXCR5 cooperatively regulate localization of Tfh cells in GCs to support GC responses. Venus-high Tfh, Venus-low Tfh, PD1-intermediate Th, PD1-low Th and naïve CD4+ T cells were sorted on FACSAria from immunized S1pr2V/+ mice or control mice for RNA extraction and hybridization on Affimetrix microarrays.
2014-05-30 | E-GEOD-56883 | 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. This SuperSeries is composed of the following subset Series: GSE21379: Expression Data from WT and Sh2d1a-/- in vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH) GSE21380: Expression Data from in vivo Tfh vs GC Tfh vs non-Tfh Refer to individual Series
2010-04-28 | E-GEOD-21381 | 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 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:Loss of Elp3 in CD4 T cells hindered the development of an optimal T follicular helper T cell (TFH) response. To understand the molecular pathway by which Elp3 is necessary for TFH responses, mice deficient for Elp3 in T cells and WT littermate were immunized with ovalbumin emulsified with complete Freund Adjuvant. 8 days later, TFH were sorted from the draining lymph nodes and submitted for RNAseq
2020-07-31 | E-MTAB-9059 | biostudies-arrayexpress