Search results for "differentiation"
showing 10 items of 1605 documents
Protein kinase CK2 enables regulatory T cells to suppress excessive TH2 responses in vivo
2014
The quality of the adaptive immune response depends on the differentiation of distinct CD4(+) helper T cell subsets, and the magnitude of an immune response is controlled by CD4(+)Foxp3(+) regulatory T cells (Treg cells). However, how a tissue- and cell type-specific suppressor program of Treg cells is mechanistically orchestrated has remained largely unexplored. Through the use of Treg cell-specific gene targeting, we found that the suppression of allergic immune responses in the lungs mediated by T helper type 2 (TH2) cells was dependent on the activity of the protein kinase CK2. Genetic ablation of the β-subunit of CK2 specifically in Treg cells resulted in the proliferation of a hithert…
Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells
2003
AbstractCoupling of ovalbumin (OVA) to anti–DEC-205 monoclonal antibody (mAb) (αDEC) induced the proliferation of OVA-specific T cells in vivo. Expansion was short-lived, caused by dendritic cells (DCs), and rendered T cells anergic thereafter. Phenotypic analysis revealed the induction of CD25+/CTLA-4+ T cells suppressing proliferation and interleukin-2 (IL-2) production of effector CD4+ T cells. The findings were supported by 2 disease models: (1) CD4+ T-cell–mediated hypersensitivity reactions were suppressed by the injection of αDEC-OVA and (2) the application of hapten-coupled αDEC-205 reduced CD8+ T-cell–mediated allergic reactions. Thus, targeting of antigens to immature DCs through …
PD-1 signalling in CD4+T cells restrains their clonal expansion to an immunogenic stimulus, but is not critically required for peptide-induced tolera…
2010
Summary The ultimate outcome of T-cell recognition of peptide–major histocompatibility complex (MHC) complexes is determined by the molecular context in which antigen presentation is provided. The paradigm is that, after exposure to peptides presented by steady-state dendritic cells (DCs), inhibitory signals dominate, leading to the deletion and/or functional inactivation of antigen-reactive T cells. This has been utilized in a variety of models providing peptide antigen in soluble form in the absence of adjuvant. A co-inhibitory molecule of considerable current interest is PD-1. Here we show that there is the opportunity for the PD-1/PD-L1 interaction to function in inhibiting the T-cell r…
Opening a Niche for Therapy: Local Lymphodepletion Helps the Immune System to Fight Melanoma
2014
In this issue, Fujiwara et al. report that local ablation of CD4+ T cells in a murine B16 melanoma model, together with concomitant activation of the immune system by OX40L, leads to complete rejection of the melanomas. Rejection was driven mainly by CD8+ T cells, which infiltrated the melanomas and secreted sizeable amounts of IFN-γ. However, CD8+ T-cell infiltration also caused the recruitment of immunosuppressive myeloid-derived suppressor cells (MDSCs). Although these cells did not prevent the rejection of the melanomas, in clinical settings the long-term repopulation of tumors by MDSCs may counteract successful treatment. Thus, local ablation of CD4+ leukocytes may improve anti-melanom…
Induction of Interleukin 10–Producing, Nonproliferating Cd4+ T Cells with Regulatory Properties by Repetitive Stimulation with Allogeneic Immature Hu…
2000
The functional properties of dendritic cells (DCs) are strictly dependent on their maturational state. To analyze the influence of the maturational state of DCs on priming and differentiation of T cells, immature CD83− and mature CD83+ human DCs were used for stimulation of naive, allogeneic CD4+ T cells. Repetitive stimulation with mature DCs resulted in a strong expansion of alloreactive T cells and the exclusive development of T helper type 1 (Th1) cells. In contrast, after repetitive stimulation with immature DCs the alloreactive T cells showed an irreversibly inhibited proliferation that could not be restored by restimulation with mature DCs or peripheral blood mononuclear cells, or by…
Dendritic Cells Lose Ability to Present Protein Antigen after Stimulating Antigen-Specific T Cell Responses, despite Upregulation of MHC Class II Exp…
2000
Abstract Immature dendritic cells (DC) take up, process and present protein antigens; mature DC are specialized for stimulating primary T cell responses with increased expression of MHC class II and co-stimulatory molecules, but are incapable of processing and presenting soluble protein. The current study examined whether maturation of DC is triggered by T cell recognition of antigens presented by immature DC. Human DC derived from CD34+ progenitor cells by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) in serum-free medium could prime naive CD4+ T cells to keyhole limpet hemocyanin (KLH) and ovalbumin (OVA). The cultured DC retained the abil…
Docosahexaenoic acid modulates the expression of T-bet and GATA-3 transcription factors, independently of PPARα, through suppression of MAP kinase ac…
2009
The present study was conducted on CD4(+) T cells, isolated from wild type (WT) and PPARalpha(null) mice, in order to assess the mechanism of action of docosahexaenoic acid (DHA), an n-3 fatty acid, in the modulation of two transcription factors, i.e., T-bet and GATA-3, implicated in T-cell differentiation towards, respectively, T(H)1 and T(H)2 phenotype. The T-cells from PPARalpha(null) mice secreted higher IFN-gamma and lower IL-4 concentrations than WT T-cells. Furthermore, the deletion of PPARalpha gene in T-cells resulted in the upregulation of T-bet and downregulation of GATA-3 both at mRNA and protein levels. DHA exerted not only an inhibitory effect on T-cell proliferation, but also…
Atypical Human Effector/Memory CD4(+) T Cells With a Naive-Like Phenotype
2018
The induction of adaptive immunological memory, mediated by T and B cells, plays an important role in protective immunity to pathogens induced by previous infections or vaccination. Naive CD4+ T cells that have been primed by antigen develop into memory or effector cells, which may be distinguished by their capability to exert a long-term and rapid response upon re-challenge by antigen, to produce distinct cytokines and surface marker expression phenotypes such as CD45RA/RO, CD27, CD62L, and CCR7. Moreover, a distinct lineage of memory T cells populates tissues (tissue-resident memory T cells or TRM cells) which orchestratea the response to pathogens re encountered at tissue sites. Recent e…
H2-M, a facilitator of MHC class II peptide loading, and its negative modulator H2-O are differentially expressed in response to proinflammatory cyto…
2000
H2-M is a major histocompatibility complex (MHC) class II-like molecule that catalyzes peptide binding to MHC class II molecules. Recently, the H2-O heterodimer, encoded by H2-Oa and H2-Ob in the MHC class II region, has been shown to be physically associated with H2-M in B cells and to downregulate H2-M function. Examination of H2-O expression in freshly isolated mouse organs revealed that H2-Oa- and H2-Ob-specific transcripts are present in both lymphoid and nonlymphoid tissues. To evaluate the gene regulation and functional impact of H2-O on antigen presentation, we examined the effects on MHCII, invariant chain (Ii), H2-M, and H2-O gene expression of interleukin (IL)-4, IL-10, and inter…
β-Catenin Signaling Drives Differentiation and Proinflammatory Function of IRF8-Dependent Dendritic Cells
2014
Abstract β-Catenin signaling has recently been tied to the emergence of tolerogenic dendritic cells (DCs). In this article, we demonstrate a novel role for β-catenin in directing DC subset development through IFN regulatory factor 8 (IRF8) activation. We found that splenic DC precursors express β-catenin, and DCs from mice with CD11c-specific constitutive β-catenin activation upregulated IRF8 through targeting of the Irf8 promoter, leading to in vivo expansion of IRF8-dependent CD8α+, plasmacytoid, and CD103+CD11b− DCs. β-Catenin–stabilized CD8α+ DCs secreted elevated IL-12 upon in vitro microbial stimulation, and pharmacological β-catenin inhibition blocked this response in wild-type cells…