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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from CD4+ and CD11c+ cells from DO11.10 RAG2-/- mice

ABSTRACT: Abatacept is a recombinant CTLA-4 moleculed fused to a mutated human IgG molecule, which is clinically used in rheumatoid arthritis by inhibiting CD28-costimulation. This study aimed to inverstigate the ability of abatacept -mediated costimulation blockade to induce antigen-specific tolerance during primary immune responses. This is important as some studies have suggested that costimulation blockade can lead to CD4+ T cell anergy which could be beneficial for early therapy of autoimmune diseases such as rheumatoid arthritis. In addition we also investigated the effect that abatacept has on CD11c+ antigen presenting cells. This is important as costimulation blocakde can affect the biderectional interaction between CD4+ T cells and CD11c+ cells influencing the immunological outcome. We used microarrays to identify if abatacept treatment leads to antigen specific anergy using transgenic animals and models of priming and oral tolerance that established a synchronised monoclonal response. In addition this magnified the effect on the CD11c+ antigen presenting cells. This study included 5 experimental groups. DO11.10 RAG2-/- mice have CD4+ T cells specific for the ovalbumin (OVA) peptide OVA323-339. These mice were immunised with CFA/OVA s.c. (primed group) or tolerised by feeding with OVA (50mg/kg) in the drinking water. CD4+ cells were isolated 10 days post immunisation from draining lymph nodes (LNs) of unimmunised (pooled LNs and Spleen), orally tolerised (mesenteric LNs), primed (axillary LNs), primed treated with control IgG (axillary LNs) and primed treated with abatacept (axillary LNs). For CD11c+ cells cells were isolated by pooled secondary lymphoid organs (LNs and spleen).

ORGANISM(S): Mus musculus

SUBMITTER: Agapitos Patakas

PROVIDER: E-GEOD-62089 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Expression data from CD4+ and CD11c+ cells from DO11.10 RAG2-/- mice

Project description:Abatacept is a recombinant CTLA-4 moleculed fused to a mutated human IgG molecule, which is clinically used in rheumatoid arthritis by inhibiting CD28-costimulation. This study aimed to inverstigate the ability of abatacept -mediated costimulation blockade to induce antigen-specific tolerance during primary immune responses. This is important as some studies have suggested that costimulation blockade can lead to CD4+ T cell anergy which could be beneficial for early therapy of autoimmune diseases such as rheumatoid arthritis. In addition we also investigated the effect that abatacept has on CD11c+ antigen presenting cells. This is important as costimulation blocakde can affect the biderectional interaction between CD4+ T cells and CD11c+ cells influencing the immunological outcome. We used microarrays to identify if abatacept treatment leads to antigen specific anergy using transgenic animals and models of priming and oral tolerance that established a synchronised monoclonal response. In addition this magnified the effect on the CD11c+ antigen presenting cells.

2014-10-07 | GSE62089 | GEO

MPS vaccination alters long-term gene expression of antigen-presenting cells in lymph nodes

Project description:Given the importance of sustained antigen presentation in maintenance of lymph node (LN) immune responses, we hypothesized that vaccine antigen availability and antigen-presenting cell (APC) populations may affect LN expansion. Compared to LNs of mice given the full MPS vaccine, LNs of mice given an MPS vaccine without antigen became prominently less enlarged and contracted sooner.To identify potential mediators of this differential, antigen-dependent response, we next focused the analysis of our scRNA-seq dataset on LN APC populations.

2024-04-05 | E-MTAB-13698 | biostudies-arrayexpress

Heterogeneity of LN resident macrophage

Project description:LN resident macrophages lining the lymphatic sinuses play critical roles in antigen capture and presentation as well as degradation. We used microarray to examine global gene expression profiles to compare SCS and med macrophages to determine the underlying molecular basis of their differential handling of antigens. Primary SCS and med macrophages were isolated and purified from LNs by flourescence-activated cell sorting and RNA extracted, amplified and hybridized for Affymetrix analysis.

2009-06-05 | E-GEOD-15767 | biostudies-arrayexpress

Immune response genes at the mRNA vaccine delivery sites and draining lymph nodes of rhesus macaques

Project description:mRNA vaccines are emerging as a powerful vaccine platform as they are well-tolerated and scalable. Modified non-replicating mRNA encoding Influenza hemagglutinin and encapsulated in lipid nanoparticles (LNP) induced robust antibody and CD4 T cell responses after intramuscular or intradermal delivery in rhesus macaques. We investigated the local innate immune responses modulating such vaccine-induced immunity at the sites of immunization (skeletal muscle and skin) and their draining lymph nodes (LNs). Rapid mobilization of antigen presenting cells was found at the LNP/mRNA-injection sites and LNs. Dendritic cells efficiently internalized the LNPs, translated the mRNA cargo and upregulated co-stimulatory molecules. In addition, several type I interferon-inducible genes were expressed at the immunization sites and draining LNs. The innate immune activation was transient and resulted in priming of antigen-specific CD4+ T cells exclusively in the vaccine-draining LNs. Collectively, mRNA-based vaccines induce type I interferon-polarized innate immunity and antigen production by antigen presenting cells, which resulted potent vaccine-specific responses.

2017-04-26 | GSE98211 | GEO

Aire regulates transfer of antigen from mTEC to dendritic cells for induction of thymic tolerance

Project description:To investigate the role of Aire in thymic selection, we examined the cellular requirements for generation of ovalbumin (OVA)-specific CD4 and CD8 T cells in mice expressing OVA under the control of the rat insulin promoter (RIP). Aire-deficiency reduced the number of mature single positive (SP) OVA-specific CD4+ or CD8+ T cells in the thymus, independent of OVA expression. Importantly, it also contributed in two way to OVA-dependent negative selection depending on the T cell type. Aire-dependent negative selection of OVA-specific CD8 T cells correlated with Aire-regulated expression of OVA. By contrast, for OVA-specific CD4 T cells, Aire affected tolerance induction by a mechanism that operated independent of the level of OVA expression, controlling access of antigen presenting cells to mTEC-expressed OVA. This study supports the view that one mechanism by which Aire controls thymic negative selection is by regulating the indirect presentation of mTEC-derived antigens by thymic dendritic cells. It also indicates that mTEC can mediate tolerance by direct presentation of Aireregulated antigens to both CD4 and CD8 T cells. Total RNA was extracted from medullary thymic epithelial cells isolated from wildtype and Aire-deficient C57BL/6 mice for comparison of gene expression profiles.

2011-04-06 | E-GEOD-28393 | biostudies-arrayexpress

Aire regulates transfer of antigen from mTEC to dendritic cells for induction of thymic tolerance

2011-04-06 | GSE28393 | GEO

Cognate T cell interactions affect the DC transcriptome [dataset 4]

Project description:Our data suggest that peptide-presenting DC receive signals from synapse-forming antigen specific CD4+ or CD8+ T cells that alter the DC expression profile. To further test this notion, we hock immunized T cell-engrafted mice with NP harboring CpG and coated with OVA (OVA / CpG NP) or the control antigen BSA (BSA / CpG NP) and isolated NP+ DC for RNAseq.

2019-04-03 | GSE129214 | GEO

Synthetically mannosylated antigens induce antigen-specific humoral tolerance and prevent anti-drug antibody responses to immunogenic biologics

Project description:The purpose of this study were to test the feasibility of using pMan-antigen therapy to induce humoral tolerance. We used OVA as a model protein along with TCR transgenic OT-I and OT-II to study antigen-specific CD4+ T cell phenotypes and transcriptomic responses using RNA-seq readouts.

2023-11-02 | GSE229893 | GEO

Gene expression analysis of mouse lymphatic endothelial cells (LECs) from the subcapsular sinus (SS, afferent) and lymphatic sinus (LS, efferent)

Project description:Afferent lymphatic vessels bring antigens and diverse populations of leukocytes to draining lymph nodes, but efferent lymphatics allow only lymphocytes to leave the nodes. Despite fundamental importance of afferent vs. efferent lymphatics in immune response and cancer spread, molecular characteristics of these different arms of the lymphatic vasculature are largely unknown. In this work we report marked transcriptional differences between afferent and efferent lymphatic endothelial cells. Mouse inguinal, axillary, and brachial lymphnodes were collected and cryomolds prepared for laser-capture microdissection. Frozen sections were stained with various cell marker antibodies and micro-dissection performed to collect lymphatic endothelial cells. Total RNA was extracted from the cells and used in microarray analysis. Alternatively, popliteal, caudal, lumbar, inguinal, mesenteric, renal, axillary, brachial, deep and superficial cervical LN were enzymatically digested, the cells stained, and FACs sorted before RNA isolation.

2016-08-24 | E-GEOD-68371 | biostudies-arrayexpress

The Serpin-like Loop-insertion of Ovalbumin Increases Stability and Reduces OVA 323-339 Epitope Immunogenicity

Project description:Chicken ovalbumin (cOVA) has been studied for decades primarily due to the robust genetic and molecular resources that are available for experimental investigations. cOVA is a member of the serpin superfamily of proteins that function as protease inhibitors, although cOVA does not exhibit this activity. As a serpin, cOVA possesses a protease-sensitive reactive-center loop that lies adjacent to the OVA 323-339 CD4+ T-cell epitope. We took advantage of the previously described single-substitution-variant, OVA R339T, which can undergo the dramatic structural transition observed in serpins to study how changes in loop size and protein stability influences CD4+ T-cell priming in vivo. We observed that the OVA R339T loop-insertion increases stability and protease resistance, resulting in reduced CD4+ T-cell priming of the OVA 323-339 epitope in SJL mice. These findings have implications for the design of more effective vaccines for the treatment of infectious diseases and cancer as well as the development of more robust CD4+ T-cell-epitope prediction tools.

2021-05-07 | PXD021756 | Pride

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