• vivo
  • The relationship of TFH cells to the Th2 lineage was confirmed when TFH cells were found to develop from CXCR5 − PD-1 − IL-4/GFP + CD4 + T cells after their transfer into naive mice and antigen challenge in vivo. (rupress.org)
  • Transcriptional profiling of TFH cells has revealed a distinct repertoire of expressed genes that demarcates them from Th1, Th2, or Th17 cells ( 3 ), and TFH cells have been reported to differentiate normally in vivo where conditions for Th1, Th2, or Th17 cell development are impaired ( 4 ). (rupress.org)
  • Using newly established triple cytokine reporter mice (Il4gfpIfngyfpIl17aFP635), we demonstrated that Il4gfp+ Th2 cells purified from in vitro cultures or isolated ex vivo from helminth-infected mice up-regulated IFNγ following adoptive transfer into Rag1-/- mice infected with P. chabaudi. (nih.gov)
  • Experimental leishmaniasis is widely used to study the effector function of Th cell subsets in vivo. (lshtm.ac.uk)
  • Here we show that infection with Th1 cell-promoting lymphocytic choriomeningitis virus (LCMV) reprogrammed otherwise stably committed GATA-3(+) Th2 cells to adopt a GATA-3(+)T-bet(+) and interleukin-4(+)interferon-gamma(+) "Th2+1" phenotype that was maintained in vivo for months. (ox.ac.uk)
  • DCs are thought to be the key professional APCs and are critical for T cell priming because transient depletion of DCs in vivo impairs naive CD4 T cell priming in most experimental settings ( 6 ). (jimmunol.org)
  • Although these findings are controversial, additional studies looking at mice in which DCs are the only cell type able to present peptide-MHCII complexes to T cells in vivo showed that Th2 development is impaired following exposure to pathogens like Trichuris muris ( 13 ) or allergens like papain ( 14 ). (jimmunol.org)
  • Together, our data suggest a key role for IFN-I to enable Th2 induction by DCs against Th2 Ag in vivo . (jimmunol.org)
  • mice
  • Hi Immunonetters, The discrimination between Th1 and Th2 phenotypes was established from data about T cell clones derived from mice. (bio.net)
  • We find that after helminth infection, or immunization with helminth antigens, reactive lymphoid organs of 4get IL-4/GFP reporter mice contain populations of IL-4/GFP-expressing CD4 + T cells that display the TFH markers CXCR5, PD-1, and ICOS. (rupress.org)
  • Consistent with a relationship between Th2 and TFH cells, IL-4 protein production, reported by expression of huCD2 in IL-4 dual reporter (4get/KN2) mice, was a robust marker of TFH cells in LNs responding to helminth antigens. (rupress.org)
  • TFH cell development after immunization failed to occur in mice lacking B cells or CD154. (rupress.org)
  • We find that in mice infected with S. mansoni , or in mice immunized with an extract of schistosome eggs, TFH cells comprise a major component of the Th cell response and express genes that would normally be considered markers of Th2 cells. (rupress.org)
  • Th1, Th2, and Th0 lines were generated from ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic mice and transferred into lymphocyte-deficient, OVA-treated severe combined immunodeficiency (SCID) mice. (jci.org)
  • Functionally, Th2 cells that up-regulated IFNγ were transcriptionally re-wired and protected recipient mice from high parasitemia. (nih.gov)
  • CD4+TCRβ+ cells were then sorted from spleens of recipient mice and treated with 10ng/mL IL-12 for 15 minutes (blue) (or untreated, red) and then stained for pSTAT4 by FACS. (nih.gov)
  • We tested the role of IL-12 by transferring naïve or Il4gfp+ Th2 cells to Rag1-/-mice and blocking IL-12 prior to and after P. chabaudi infection (Fig 7C). (nih.gov)
  • Specific ablation of Atg16l1 in Foxp3(+) Treg cells in mice demonstrated that autophagy directly promotes their survival and metabolic adaptation in the intestine. (ox.ac.uk)
  • In the study presented here, a stable cell surface marker expressed on Th2 cells, T1/ST2, has been used to assess the distribution of CD4(+)T1/ST2(+) T cells in different organs of healer and nonhealer strains of mice during the course of L. major infection. (lshtm.ac.uk)
  • however, CD4(+) T1/ST2(+) T cells could be enriched from the lymphoid organs of infected nonhealer but riot from healer strains of mice. (lshtm.ac.uk)
  • The highest frequency of CD4(+) T1/ST2(+)T cells was detected in the footpads of mice with nonhealing disease, showing that CD4(+) T1/ST2(+) T cells home to the footpads. (lshtm.ac.uk)
  • The number of Th2-type effector iNKT cells is variable in different strains of mice, and their number impacts CD8 T, dendritic, and B cell function. (rupress.org)
  • Similarly, CD4+ T cells purified from ICOS-/- mice immunized with the protein keyhole limpet hemocyanin (KLH) in alum or complete Freund's Adjuvant have attenuated IL-4 secretion, but similar IFN-g and IL-5 secretion when recalled with KLH. (wikipedia.org)
  • IL-33 is constitutively located in the nucleus of structural cells of humans and mice and has a helix-turn-helix domain presumably allowing it to bind to DNA. (wikipedia.org)
  • Studies of the similar gene in mice suggested that this cytokine may be a proinflammatory cytokine favoring Th2-type immune response. (wikipedia.org)
  • lineages
  • The original Th1/Th2 dichotomy has expanded to include a minimum of four different CD4 T cell lineages, with the concept of neatly pigeonholed irreversibly differentiated lineages requiring some reassessment with recent findings of plasticity and intermediate phenotypes among various CD4 lineages ( 4 , 5 ). (jimmunol.org)
  • antigens
  • Persistent wheezing in children is predicted by development of IgE-mediated hypersensitivity to inhaled allergens ( 5 ), indicating that the development of an inappropriate adaptive Th2-polarized immune response to environmental antigens plays a critical role in the development of asthma. (jci.org)
  • We have discovered a previously unrecognized role for Type I IFN (IFN-I) in the optimal activation and function of DCs following exposure to strongly Th2-polarizing antigens. (jimmunol.org)
  • Invariant NKT cells (iNKT cells) are a subset of TCRαβ + T cells that recognize glycolipid antigens in the context of the unconventional major histocompatibility complex class I protein CD1D. (rupress.org)
  • Ability of TAMs to present tumour-associated antigens is decreased as well as stimulation of the anti-tumour functions of T and NK cells. (wikipedia.org)
  • lineage
  • However, the lineage relationship of TFH cells to the other Th subsets remains unclear. (rupress.org)
  • Collectively, these data suggest that TFH cells constitute a distinct lineage. (rupress.org)
  • Consistent with this, our data suggest TFH cells can differentiate from within the Th2 lineage, and that this process is germinal center dependent. (rupress.org)
  • These findings demonstrate Th2 lineage heterogeneity, in which the IL5 gene is regulated in a hierarchical manner relative to other Th2 genes. (jimmunol.org)
  • Since the first description of Th1 and Th2 cells, a large body of data has established the basic paradigm of CD4 T cell lineage heterogeneity, with each lineage having distinct molecular, cellular, and functional properties ( 1 - 3 ). (jimmunol.org)
  • However, knowledge on the plasticity of Th2 cell lineage commitment is limited. (ox.ac.uk)
  • Stable coexpression of GATA-3 and T-bet provides a molecular concept for the long-term coexistence of Th2 and Th1 cell lineage characteristics in single memory T cells. (ox.ac.uk)
  • Each of these T cell subsets exhibits different functional properties, and the development of each lineage is programmed by a distinct transcription factor ( 4 ). (jimmunol.org)
  • Expression of the semi-invariant iNKT cell TCR, comprised of an invariant TCRα chain (Vα14Jα18) paired with a biased TCR Vβ repertoire (Vβ8, -7, and -2), allows for recognition of glycolipid-CD1D complexes on neighboring cortical DP thymocytes, which results in their selection into the iNKT cell lineage. (rupress.org)
  • phenotype
  • On the other hand, induction of the T H 2 phenotype from naïve CD4 + T cells requires IL-4 binding of the functional IL-4 receptor and activation of STAT6. (sciencemag.org)
  • Thus, T H 2 cells are resistant to T H 1 conversion, and decreased expression of IL-12Rβ2 is not necessary for the establishment of the T H 2 phenotype. (sciencemag.org)
  • epithelial cells
  • The mucus also facilitates passage of the luminal contents along the length of the intestines, protects the epithelial cells from digestive enzymes, and prevents the direct contact of microorganisms with the epithelial layer. (wikipedia.org)
  • It consists of the layer of epithelial cells lining the intestine. (wikipedia.org)
  • Specialised secretory epithelial cells called Paneth cells secrete abundant quantities human α-defensins into the intestinal lumen of healthy individuals. (wikipedia.org)
  • Secretory immunoglobulin A (sIgA) is produced by plasma cells in the lamina propria and transported into the lumen by intestinal epithelial cells. (wikipedia.org)
  • SIgA blocks epithelial-specific receptors on pathogens, thereby preventing their attachment to epithelial cells. (wikipedia.org)
  • inflammatory
  • Various adhesion molecules are involved in the local recruitment of T cells and other inflammatory cells. (bvsalud.org)
  • The Th1/Th2 paradigm also has particular relevance for certain inflammatory diseases, as asthma is essentially a Th2 response gone awry, and many autoimmune diseases depend on a Th1 response to autoantigens. (rupress.org)
  • receptor
  • Additionally, the authors found that the IL-12 receptor-bearing T H 2 cells continued to synthesize IL-4 even in the presence of IL-12 in the growth medium. (sciencemag.org)
  • Th2 cell reprogramming required T cell receptor stimulation, concerted type I and type II interferon and interleukin-12 signals, and T-bet. (ox.ac.uk)
  • In this issue, two groups have provided one of the best examples of this concept, by identifying CXCR5 as a chemokine receptor responsible for the follicular homing of a unique subset of T helper cells for antibody production ( 13 )( 14 ). (rupress.org)
  • T and B cells continuously recirculate from blood to lymphoid tissue, gaining entry through their expression of L-selectin and the chemokine receptor CCR7. (rupress.org)
  • Here we demonstrate a unique function for the transcription factor lymphoid enhancer factor 1 (LEF1) in the postselection expansion of iNKT cells through a direct induction of the CD127 component of the receptor for interleukin-7 (IL-7) and the transcription factor c- myc . (rupress.org)
  • The protein encoded by this gene belongs to the CD28 and CTLA-4 cell-surface receptor family. (wikipedia.org)
  • PD-L1 binds to its receptor, PD-1, found on activated T cells, B cells, and myeloid cells, to modulate activation or inhibition. (wikipedia.org)
  • DP2 was found to stimulate the directed movement or chemotaxis of human T-helper type 2 cells (see T helper cell#Th1/Th2 Model for helper T cells) by binding to a receptor initially termed GPR44 and thereafter CRTH2 (for Chemoattractant Receptor-homologous molecule expressed on T-Helper type 2 cells). (wikipedia.org)
  • As evidenced by its initial discovery as a receptor for PGD2 in T-helper type 2 cells, activated DP2 triggers Gi alpha subunit-linked heterotrimeric G proteins to dissociate into their component a) Gi alpha subunits (also termed Giα subunits) which simulate phospholipase C to cleave phosphatidylinositol triphosphate into inositol triphosphate (IP3) and diacylglycerol (DAG) and b) G beta-gamma complex of subunits (Gβγ) which inhibit adenyl cyclase. (wikipedia.org)
  • Like all T cells, they express the T cell receptor-CD3 complex. (wikipedia.org)
  • The T cell receptor (TCR) consists of both constant and variable regions. (wikipedia.org)
  • Numbers of molecules enhance or dampen IL-9 production and contribute to TH9 development such as: Activin A that can fully substitute the role of TGF-β in TH9 cells, then Jagged2, programmed cell death ligand (PD-L2), cyclooxy- genase (COX)-2, 1,25-dihydroxyvitamin D3, calcitonin gene-related peptide (CGRP), tumor necrosis factor receptor superfamily member 4 (TNFRSF4 or OX40), and thymic stromal lymphopoietin (TSLP). (wikipedia.org)
  • This gene encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind interleukin 4 and interleukin 13 to regulate IgE antibody production in B cells. (wikipedia.org)
  • They are required for binding of interleukin-4 to the receptor alpha chain, which is a crucial event for the generation of a Th2-dominated early immune response. (wikipedia.org)
  • genes
  • As acceptance of the Th1/Th2 paradigm increased among immunologists, so too has the effort to identify Th1- or Th2-associated genes or molecules. (rupress.org)
  • The gene encodes for a transcription factor that belongs to the Hairy/Enhancer of Split (Hes) subfamily of basic helix-loop-helix factor genes which encode transcriptional repressors that function as downstream targets to regulate cell fate during tissue development. (wikipedia.org)
  • PcG gene products form complexes via protein-protein interaction and maintain the transcription repression of genes involved in embryogenesis, cell cycles, and tumorigenesis. (wikipedia.org)
  • allergic
  • These results indicate that antigen-specific Th1 cells may not protect or prevent Th2-mediated allergic disease, but rather may cause acute lung pathology. (jci.org)
  • The evidence, however, demonstrating that Th1 cells actually render salutary effects in allergic disease and asthma, is indirect. (jci.org)
  • In this study, we demonstrate that STAT6 in bone marrow-derived myeloid cells was sufficient for the production of CCL17, CCL22, CCL11, and CCL24 and for Th2 lymphocyte and eosinophil recruitment into the allergic airway. (jimmunol.org)
  • TH9 cells are present in the peripheral blood of allergic patients while such a population is rare in non-allergic persons. (wikipedia.org)
  • gene
  • The Th2 gene locus is located on human chromosome 5q31 and mouse chromosome 11. (jimmunol.org)
  • Inducible T-cell costimulator is an immune checkpoint protein that in humans is encoded by the ICOS gene. (wikipedia.org)
  • The expression of this gene was detected in various tumor cells, but is limited in neural organs in normal tissues. (wikipedia.org)
  • IRF4 binds to the promoter of Il-9 gene in TH9 cells and it is dependent on STAT6. (wikipedia.org)
  • subsets
  • The relationship of T follicular helper (TFH) cells to other T helper (Th) subsets is controversial. (rupress.org)
  • Our studies in this area have, on the basis of surface marker expression, identified subsets of Th2 cells ( 15 ), one of which is notable for its expression of PD-1, a molecule that has been reported to be expressed by TFH cells ( 6 ). (rupress.org)
  • Cell surface molecules that reliably mark Th1 or Th2 cells were also sought, and to date the chemokine receptors are probably the most convenient (although by no means ideal) markers of functional subsets. (rupress.org)
  • binds
  • GATA-3 binds to the Th2 locus control region as well as the IL5 promoter ( IL5p ) and IL13p ( 9 ). (jimmunol.org)
  • It binds to CD40 on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. (wikipedia.org)
  • When a Th cell encounters and recognises the antigen on an APC, the TCR-CD3 complex binds strongly to the peptide-MHC complex present on the surface of professional APCs. (wikipedia.org)
  • airway
  • In contrast, STAT6 in airway-lining cells did not mediate chemokine production or support cellular recruitment. (jimmunol.org)
  • induction
  • LCMV-triggered T-bet induction in adoptively transferred virus-specific Th2 cells was crucial to prevent viral persistence and fatal immunopathology. (ox.ac.uk)
  • plasticity
  • In summary, this study demonstrates that Th2 cells retain substantial plasticity with the ability to produce IFNγ during Plasmodium infection. (nih.gov)
  • protein
  • T cell lines specific for purified protein derivative or streptokinase (SK) derived in the presence of P exhibited significant increased ability to produce IL-5 in comparison with T cell lines derived in the absence of P. Moreover, IL-4 was significantly increased in SK-specific T cell lines derived in the presence of P in comparison with SK-specific T cell lines derived in the absence of this hormone. (jimmunol.org)
  • Mature Th cells express the surface protein CD4 and are referred to as CD4+ T cells. (wikipedia.org)
  • CD154, also called CD40 ligand or CD40L, is a cell surface protein that mediates T cell helper function in a contact-dependent process and is a member of the TNF superfamily of molecules. (wikipedia.org)
  • Sealing of the space between adjacent cells is mediated by junctional complexes formed by protein connections elaborated by each individual cell. (wikipedia.org)
  • pathway
  • Although we know much about the molecular cues that initiate development of Th1 cells, Tregs, and Th17 cells ( 4 ), our understanding of the signals that initiate the Th2-developmental pathway are less clear, despite almost three decades of intense study. (jimmunol.org)
  • Crucial for forming an effective barrier is the precise control of the paracellular pathway (a route for translocation of molecules between cells). (wikipedia.org)
  • mediate
  • Once activated, phosphorylated STAT6 mediate the transcription of Gata3 and Irf4, which are both necessary for polarization of TH9 cells. (wikipedia.org)
  • molecules
  • Effective priming of naive CD4 T cells is dependent on "professional" APCs that express costimulatory molecules and present Ag-derived peptides complexed with MHC class II (MHCII) ( 5 ). (jimmunol.org)
  • With the assistance of a phosphatase present on the intracellular section of CD45 (common leukocyte antigen), these molecules activate major Th cell intracellular pathways. (wikipedia.org)
  • The mucus consists of a highly glycosylated hydrated gel formed by mucin molecules that are secreted by goblet cells. (wikipedia.org)
  • The mucus prevents large particles from contacting the epithelial cell layer while allowing small molecules to pass. (wikipedia.org)
  • Antimicrobial peptides (AMPs), which are a diverse array of molecules that kill bacteria and fungi, are secreted by Paneth cells into the lumen. (wikipedia.org)
  • transcription
  • LEF1 also directly augments expression of the effector fate-specifying transcription factor GATA3, thus promoting the development of Th2-like effector iNKT cells that produce IL-4, including those that also produce interferon-γ. (rupress.org)
  • STAT6 repress the expression of transcription factors T-bet and Foxp3 in TH9 cells, that normally block IL-9 production. (wikipedia.org)
  • GATA3
  • STAT6, IRF4, GATA3 are absolutely required for TH9 cell development and other such as PU.1, BATF, NF-κB, NFAT1, STAT5, AP-1 contribute to TH9 sub-population commitment and to IL-9 production. (wikipedia.org)
  • antigen
  • Th1-mediated neutrophil and Th2-mediated eosinophil accumulation in the large intestine, which occurred after intrarectal challenge with the antigen, was indicated by the significant elevation of myeloperoxidase (MPO) and eosinophil peroxidase (EPO) activity. (bvsalud.org)
  • Activated T cells migrate to the B cell follicles and position themselves at the edge of the follicle, where they meet antigen-primed B cells that have also specifically migrated outwards. (rupress.org)
  • Thereafter, antigen-primed T cells become distributed throughout the entire follicle, presumably to egg on the germinal center reaction. (rupress.org)
  • PD-L1 binding to PD-1 also contributes to ligand-induced TCR down-modulation during antigen presentation to naive T cells, by inducing the up-regulation of the E3 ubiquitin ligase CBL-b. (wikipedia.org)
  • For example, when an antigen-presenting cell expresses an antigen on MHC class II, a CD4+ cell will aid those cells through a combination of cell to cell interactions (e.g. (wikipedia.org)
  • Naïve T cells are those T cells that have never been exposed to the antigen that they are programmed to respond to). (wikipedia.org)
  • The variable region determines what antigen the T cell can respond to. (wikipedia.org)
  • Class II MHC proteins are generally only found on the surface of specialised antigen-presenting cells (APCs). (wikipedia.org)
  • During an immune response, professional antigen-presenting cells (APCs) endocytose foreign material (typically bacteria or viruses), which undergoes processing, then travel from the infection site to the lymph nodes. (wikipedia.org)
  • Once at the lymph nodes, the APC begin to present antigen peptides that are bound to Class II MHC, allowing CD4+ T cells that express the specific TCRs against the peptide/MHC complex to activate. (wikipedia.org)
  • Upon subsequent encounters with a given antigen, memory T cells are re-activated using the same TCR pathways. (wikipedia.org)
  • inhibit
  • Cytostatics inhibit cell division. (wikipedia.org)
  • The role of TH9 cells is not absolutely clear yet but so far it seems that they main physiological role is defense against helminthis infections and it was also shown that TH9 cells are able to inhibit melanoma cells growth. (wikipedia.org)
  • respectively
  • These results demonstrate that IL-5 + and IL-5 − Th2 cells, respectively, represent more and less highly differentiated Th2 cell subpopulations. (jimmunol.org)
  • In contrast, the migration of Th1 cells and neutrophils was diminished by blockage of αL/ß2-integrin and ICAM-1, respectively. (bvsalud.org)
  • antibody
  • However, this neat scheme had one troubling aspect: where do helper cells for antibody production fit in? (rupress.org)
  • T cell help for antibody production has long been considered a Th2 property ( 2 )( 3 ), although certain Ig class switching relies on IFN-γ. (rupress.org)
  • This diminishes both B cell clone expansion and antibody synthesis. (wikipedia.org)
  • Tonsillar (relating to palatine tonsil) B cells can mature to produce all the five major Immunoglobulin (Ig, aka antibody) classes. (wikipedia.org)
  • induces
  • showed that PD-1, up-regulated on activated CD4 T-cells, can bind to PD-L1 expressed on monocytes and induces IL-10 production by the latter. (wikipedia.org)
  • optimal
  • Mechanistically, TCR stimulation and responsiveness to IL-12 and IFNγ, but not type I IFN, was required for optimal IFNγ production by Th2 cells. (nih.gov)
  • Further, Th2-promoting DCs depended on IFN-I signaling for optimal activation, efficient migration to the draining LN, and effective localization within the T cell zone. (jimmunol.org)