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CD4+ follicular regulatory T cells optimize the influenza virus-specific B cell response

ABSTRACT: CD4+ follicular regulatory T cells optimize the influenza virus-specific B cell response

PROVIDER: PRJNA679464 | ENA |

REPOSITORIES: ENA

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CD4+ follicular regulatory T cells optimize the influenza virus-specific B cell response

Project description:CD4+ follicular regulatory T cells (Tfr cells) control B cell responses through the modulation of follicular helper T (Tfh) cells and germinal center development, while suppressing autoreactivity; however, their role in the regulation of productive germinal center B cell responses and humoral memory is incompletely defined. We show that Tfr cells promote antigen-specific germinal center B cell responses upon influenza virus infection. Following viral challenge, we found that Tfr cells are necessary for robust generation of virus-specific, long-lived plasma cells, antibody production against both hemagglutinin (HA) and neuraminidase (NA), the two major influenza virus glycoproteins, and appropriate regulation of the BCR repertoire. To further investigate the functional relevance of Tfr cells during viral challenge, we utilized a sequential immunization model with repeated exposure of antigenically partially conserved strains of influenza viruses, revealing that Tfr cells promote recall antibody responses against the conserved HA stalk region. Thus, Tfr cells promote antigen-specific B cell responses and are essential for the development of long-term humoral memory.

2020-11-20 | GSE161788 | GEO

CD4+ follicular regulatory T cells optimize the influenza virus-specific B cell response.

Project description: Not available

| S-EPMC7748821 | biostudies-literature

Transcription profiling of mouse vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH)

Project description:Analysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) follicular helper CD4 T cells (CXCR5high),versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection. A paper including data analysis of these experiments has been accepted for publication (Robert J. Johnston et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of follicular helper CD4 T cell differentiation). Experiment Overall Design: Analysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) follicular helper CD4 T cells (CXCR5high), versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection.

2009-08-07 | E-GEOD-16697 | biostudies-arrayexpress

Deciphering and predicting CD4+ T cell immunodominance of Influenza virus hemagglutinin

Project description:The importance of CD4+ T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naïve and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naïve and memory CD4+ T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naïve CD4+ T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry-based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naïve T cells specific for cryptic H1-HA peptides, and demonstrate that antigen processing represents a major constraint determining immunodominance.

2020-06-29 | PXD018151 | Pride

Transcription profiling of WT and NFAT2 KO follicular helper CD4 T cells and non follicular helper CD4 T cell populations

Project description:Comparatative gene expression analysis for wild type and NFAT2-/- CD4 T cell subsets including follicular helper CD4+ T (TFH) cells, activated CD4+ T cells, and naive CD4+ T cells isolated from the spleen.

2014-02-21 | E-MEXP-3820 | biostudies-arrayexpress

Expression Data from in vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH)

2009-07-28 | GSE16697 | GEO

Expression data from primary and secondary CD4 T cell effectors responding towards influenza A virus infection

Project description:How secondary CD4 T cell effectors, derived from resting memory cells, differ from primary cells, derived from naïve precursors, and how such differences impact recall responses to pathogens is unknown. We used microarrays to detail the global programme of gene expression underlying differences between primary and secondary CD4 T cell effectors purified from the spleen, dLN, and lung on day 7 following A/PR8/34 influenza infection. Congenic naïve or in vivo influenza primed memory HNT TCR trangenic CD4 T cells were sort purifed from the spleens, dLNs, and lungs of infected mice on day 7 post infection for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain only CD4 T cell populations that had entered into the immune response by also sorting and collecting only those cells that had divided at least 5 times by CFSE analysis.

2012-08-27 | E-GEOD-40230 | biostudies-arrayexpress

Expression Data from WT and Sh2d1a-/- in vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH)

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

Expression data from primary and secondary CD4 T cell effectors responding towards influenza A virus infection

2012-08-27 | GSE40230 | GEO

Expression data from NKG2A/C/E+ and negative CD4 effectors after influenza A infection

Project description:CD4 T cells can differentiate into a hetergenous population of effector T cells. A population of cytotoxic CD4 T cells can be generated against influenza challenge, however identifying these cells have been challenging. The expression of NKG2A/C/E on CD4 T cells identifies CD4 T cells with cytotoxic potential thus allowing further characterization of this subset of CD4 effector cells. Microarray analysis comparing cytotoxic CD4 T cells versus non-cytotoxic CD4 T cells reveals unique differences in localization between these populations in the lung after influenza A challenge.

2016-11-08 | GSE89634 | GEO

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