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  • transgenic mice
  • The incidence of disease was reduced 2-fold in transgenic mice raised under specific pathogen-free conditions, suggesting a role for infectious agents. (aacrjournals.org)
  • Studies of the small intestines of transgenic mice showed that the subepithelial basement membranes (BM) were highly abnormal and that they exhibited heightened expression of genes involved in immune responses. (aacrjournals.org)
  • Generation of collagen XIII Col13a1 del transgenic mice and their health monitoring. (aacrjournals.org)
  • More than half of the double-transgenic mice spontaneously developed autoimmune demyelination in their spinal cords and optic nerves, exhibiting pathologies reminiscent of human MS. The studies describe an important new model for MS research. (jci.org)
  • Female thy1.1 + pmel-1 TCR transgenic mice were generated in our laboratory ( 35 ) and made available online ( http://www.jax.org ). (aacrjournals.org)
  • 1997. Ly49A transgenic mice provide evidence for a major histocompatibility complex-dependent education process in NK cell development. (berkeley.edu)
  • Tregs
  • The frequency and function of Tregs in NOD and NOR mice were also equivalent. (diabetesjournals.org)
  • There are 2 broad categories of Tregs that function in different immunological settings depending upon the context of antigen exposure and the nature of the inflammatory response. (jci.org)
  • Thus, killing of encephalitogenic CD4 + T cell lines in vitro by cytotoxic CD8 + as well as neutralization of their capacity in vivo to cause EAE clearly indicated that CD8 + Tregs recognizing some cell surface molecules on vaccinating CD4 + can be induced. (jci.org)
  • Constitutive expression of the forkhead box protein 3 transcription factor (Foxp3 in mice and FOXP3 in humans) is necessary for Tregs to regulate self-tolerance ( 8 , 9 ). (frontiersin.org)
  • induced Tregs (iTregs) upregulate FOXP3 in the periphery following antigen exposure and, for example, stimulation from transforming growth factor β (TGF-β) ( 24 ). (frontiersin.org)
  • foreign antigens
  • These mechanisms ensure induction of effective but appropriately limited responses against foreign antigens while preventing autoreactivity from inflicting escalating damage. (jci.org)
  • While the primary function of T cells is to mediate protective immune responses to foreign antigens presented by self-MHC, T cells respond robustly to antigenic differences in allogeneic tissues. (jove.com)
  • responses
  • In conjunction with the H2 g7 MHC, other Idd genes are also required to interactively contribute to the development of diabetogenic T-cell responses in NOD mice ( 1 ). (diabetesjournals.org)
  • The mycolyl transferase antigen 85 complex is a major secreted protein family from mycobacterial culture filtrate, demonstrating powerful T cell stimulatory properties in most HIV-negative, tuberculin-positive volunteers with latent M.tuberculosis infection and only weak responses in HIV-negative tuberculosis patients. (hindawi.com)
  • Mice are the experimental tool of choice for the majority of immunologists and the study of their immune responses has yielded tremendous insight into the workings of the human immune system. (jimmunol.org)
  • First, immune responses targeted against unique antigens theoretically would be exquisitely tumor-specific and produce no collateral damage to normal cells. (pnas.org)
  • DTH responses can be induced to various antigens, for example ovalbumin, tuberculin, tetanus toxoid, or keyhole limpet hemocyanin (KLH). (jove.com)
  • This information may then be used to develop antigen-specific therapies for type 1 diabetes and assays to monitor changes in pathogenic, beta cell-specific T cell responses. (springer.com)
  • Neoepitopes that are known targets of pathogenic T cell responses will be prime candidates for incorporation into antigen-specific therapies to restore immune tolerance to beta cells. (springer.com)
  • 1994. The role of IL-6, IL-1 and CD28-signaling in responses of mouse CD4+ T cells to immobilized anti-TCR mAb. (berkeley.edu)
  • induce
  • The failure of NOR CD4 T-cells to induce type 1 diabetes was not due to decreased proliferative capacity of BDC2.5 clonotypic-like cells. (diabetesjournals.org)
  • This is accomplished either through the injection of mutant human mRNA to induce dominant negative or gain of function alleles, or utilization of morpholino (MO) antisense oligonucleotides to suppress genes to mimic loss of function variants. (jove.com)
  • Acute viral infections typically induce a CD4 + T cell response that is almost exclusively composed of Tfh and Th1 cells, in approximately equal proportion. (frontiersin.org)
  • vitro
  • 7-10 d after immunization of SWXJ mice with PLP 139-151, primed LN cells were reactivated in vitro with PLP 139-151 (25 μg/ml). (rupress.org)
  • Three essential tools developed in cattle and used for the control of human tuberculosis (TB) include (1) vaccination with an attenuated Mycobacterium bovis Bacillus Calmette Guerin (BCG, [ 1 ]), (2) use of tuberculin as an in vivo diagnostic reagent, and (3) antigen-induced interferon- (IFN-) γ as an in vitro biomarker of TB infection. (hindawi.com)
  • or (3) by immunizing mice that cxpivss transyenie HLA genes, isolating T-cell hybridomas specific for proinsulin and analyzing their specificity in vitro. (allindianpatents.com)
  • molecule
  • Polymorphisms of cytotoxic T-lymphocyte antigen 4 (CTLA-4) - a co-signaling molecule with vital importance to Treg function ( 10 ) - are also linked to autoimmunity ( 11 ). (frontiersin.org)
  • In NOD mice, a structurally similar class II MHC molecule, I-Ag7, contributes to disease susceptibility (reviewed in refs. (100md.com)
  • In terms of suppressive pathways, multiple possibilities have been described, such as immunosuppressive cytokines, contact-dependent cytotoxicity, metabolic disruption, and suppression of antigen presenting cells via co-inhibitory molecule expression. (frontiersin.org)
  • In an attempt to provide a mouse model for these diseases, a hybrid MHC class II molecule between the peptide binding domains of human HLA-DRA and HLA-DRB*0401 and the membrane proximal domains of mouse I-E (H2-E) was engineered and co-injected into C57BL/6 fertilized eggs. (taconic.com)
  • Adoptive
  • RESEARCH DESIGN AND METHODS- Adoptive transfer and bone marrow chimerism approaches tested the diabetogenic activity of CD4 and CD8 T-cells from NOR mice and NOD stocks congenic for NOR-derived Idd resistance loci. (diabetesjournals.org)
  • Female C57BL/6 mice and C57BL/6 TCR-α −/− mice (obtained from The Jackson Laboratory) bearing B16, an H-2 b+ /gp100 + murine melanoma, established and maintained as previously described ( 36 ), were used as recipients for adoptive immunotherapies. (aacrjournals.org)
  • bone marrow
  • However, bone marrow chimerism experiments demonstrated that intrinsic factors inhibited the pathogenic activity of NOR CD4 T-cells. (diabetesjournals.org)
  • We have previously shown that both mature and UCA gp41 MPER bnAb heavy- (HC) and light-chain (LC) gene-rearranged (V H DJ H /V L J L ) KI mice have severe bone marrow (BM) deletion, and the few remaining B cells in the periphery are anergic, resulting in massive reduction in BM precursor frequency of MPER bnAbs 16 . (nature.com)
  • lymphoid
  • Proinsulin is the major product of β cells and, with the possible exception of rare self-antigen-expressing cells in lymphoid tissues ( 5 ), is the only known T1D autoantigen that is expressed exclusively in β cells. (rupress.org)
  • One difference worth noting is that whereas mice have significant bronchus-associated lymphoid tissue, this is largely absent in healthy humans ( 9 ), possibly reflecting a higher breathable Ag load for animals living so much closer to the ground. (jimmunol.org)
  • In mouse and human secondary lymphoid organs, Tfh cells are characterized by the expression of CXCR5, the costimulatory molecules ICOS, PD-1 and OX40, and the transcriptional repressor Bcl-6 [ 1 - 3 ]. (plos.org)
  • assays
  • Progress in understanding the mechanism of CD4/CD8 lineage commitment would be advanced by assays to assess the early stages of lineage commitment. (rupress.org)
  • For translational research, this information will support the development of assays that can monitor changes in the function and frequency of antigen-specific T cells from a blood sample. (springer.com)
  • immunity
  • The conservation of the integrity of this unusual DR allelic pair suggests some selective advantage which is likely to be associated with the presentation of pathogen antigen to T-cells and the induction of protective immunity. (jove.com)
  • T follicular helper (Tfh) cells play an essential role in the development of antigen-specific B cell immunity. (plos.org)
  • First, cross-protective immunity requires that some fraction of the CD4 T cells elicited by seasonal viruses be specific for peptide epitopes that are shared by seasonal and pandemic strains. (pubmedcentralcanada.ca)
  • We chose to genetically engineer tumor antigen-specific CD8 + T cells to secrete interleukin (IL)-12, a potent proinflammatory and antiangiogenic cytokine capable of activating multiple aspects of innate and adaptive antitumor immunity ( 11 - 20 ). (aacrjournals.org)
  • genetically
  • Taken together, these data indicate the autoreactive T cells can be genetically designed to produce therapeutic factors in an antigen-inducible manner resulting in a decreased severity of clinical and histological autoimmune demyelinating disease. (rupress.org)
  • Thus, our strategy was to modify T cells genetically for delivering therapeutic factors in a nonconstitutive, antigen-inducible manner during an autoimmune disease. (rupress.org)
  • Clearly, with so many paradigms that translate well between the species, and with the relative ease with which mice can now be genetically manipulated, mouse models will continue to provide important information for many years to come. (jimmunol.org)
  • proinsulin
  • NOD mice with a genetic deletion of both native insulin genes ( Ins1 and Ins2 ) expressing a mutated nonimmunogenic but hormonally active proinsulin transgene (dKO/B16:A mice) do not develop T1D, demonstrating that immunologic recognition of insulin is crucial for the initiation of diabetes in this model ( 3 ). (diabetesjournals.org)
  • Several lines of evidence implicate proinsulin as a target autoantigen in T cell-mediated β cell destruction in humans and the NOD mouse model of T1D ( 4 ). (rupress.org)
  • NOD mice that transgenically express proinsulin under the control of an MHC class II promoter are protected from diabetes ( 10 , 11 ). (rupress.org)
  • NOD mice with targeted disruptions of the proinsulin I and II genes have a decreased ( 12 ) and increased ( 13 ) incidence of diabetes, respectively. (rupress.org)
  • Furthermore, diabetes did not develop in NOD mice that expressed a mutated proinsulin I (Y to A at B16) ( 14 ). (rupress.org)
  • Here, we sought to define the specificity of proinsulin-specific CD4 + T cells in T1D. (rupress.org)
  • Proinsulin is an important antigen in early diabetes. (soc-bdr.org)
  • repertoire
  • The numbers of I-Ag7 Crestricted CD4+ T cells are diminished in Cat L Cdeficient mice, although a potentially diabetogenic T cell repertoire persists. (100md.com)
  • We also discuss the application of neoepitopes to the development of antigen-specific therapies for type 1 diabetes and the unresolved challenges that need to be overcome before the full repertoire of neoepitopes recognised by pathogenic human T cells in type 1 diabetes can be determined. (springer.com)
  • interleukin-10
  • Lymph node cells from (SWR×SJL)F 1 mice immunized with the p139-151 determinant of myelin proteolipid protein (PLP) were transfected with a DNA construct that placed the anti-inflammatory cytokine interleukin-10 (IL-10) cDNA under control of an antigen-inducible IL-2 promoter region. (rupress.org)
  • subset
  • Included in this subset will be differences that may preclude a successful preclinical trial in mice becoming a successful clinical trial in human. (jimmunol.org)
  • peripheral
  • HP allows the remaining peripheral T cell specificities to regenerate the diminished lymphocyte compartment. (jimmunol.org)
  • Rather, Cat L Cdeficient mice display a defect in the generation of CD4+ T cells that leads to an increase in the proportion of CD4+CD25+ T cells in the peripheral CD4+ T cell compartment compared with that in wild-type controls. (100md.com)
  • In contrast, the precursor frequency of CD4-mimicking type of CD4-binding site bnAbs (VRC01-class) has been found to be normal in UCA KI mice in one study 9 , but abnormal with BM deletion, receptor editing, and peripheral anergy in another 17 . (nature.com)
  • pathogenic
  • OBJECTIVE- Although the H2 g7 major histocompatibility complex (MHC) provides the primary pathogenic component, the development of T-cell-mediated autoimmune type 1 diabetes in NOD mice also requires contributions from other susceptibility ( Idd ) genes. (diabetesjournals.org)
  • In addition, the pathogenic activity of NOR B-cells is significantly lower than those of NOD origin because of contributions from Idd9 / 11 region genes on Chr4 ( 12 ). (diabetesjournals.org)
  • The majority of our knowledge of these pathogenic processes is derived from the NOD mouse model, although some processes are mirrored in the human disease. (soc-bdr.org)
  • islet
  • Pubmed ID: 16493034 Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is recognized as a major autoantigen for autoimmune type 1 diabetes (T1D) in the NOD mouse model. (jove.com)
  • T cells within insulitis are specific for islet antigens rather than bystanders. (soc-bdr.org)
  • tumor
  • This suggested that collagen XIII might normally function as a novel tumor suppressor gene for intestinal microbe-dependent lymphomas. (aacrjournals.org)
  • These results were taken to imply that unique antigens specific to a particular tumor were more "immunogenic" than shared antigens that would be expressed by multiple different tumors. (pnas.org)
  • From the standpoint of immunotherapy, the concept of targeting unique tumor-specific antigens provided two fundamental advantages. (pnas.org)
  • These potential advantages are balanced against a significant disadvantage, namely that immune therapies targeted against unique tumor-specific antigens would by necessity be individualized rather than generic, thereby dramatically increasing the cost and labor intensity of treating large numbers of patients. (pnas.org)
  • In this study, we examined the effects of delivering IL-12 directly to the tumor site by adoptively transferring tumor-specific gene-engineered CD8 + T cells. (aacrjournals.org)
  • T-cell receptor (TCR) specificity was critical for tumor regression, suggesting that arrested migration of T cells at the tumor site was essential for successful treatments. (aacrjournals.org)
  • deletion
  • In previous studies, mice that were homozygous for a transgene ( Col13a1 del ) expressing mutant collagen XIII with a partial deletion of the collagenous ectodomain died in utero of cardiovascular defects ( 17 , 18 ). (aacrjournals.org)
  • Clone
  • Indeed, the ratio of Tfh to Th1 cells in the CD4 + T cell response to acute lymphocytic choriomeningitis virus (LCMV) has been amply reported close to 1 and 2 for LCMV Armstrong ( 9 - 14 ) and clone 13 (Cl13) ( 15 - 19 ), respectively, and similar results were also reported for influenza A virus infection ( 20 - 23 ). (frontiersin.org)
  • Clone REA828 recognizes mouse CD62L, also known as L-selectin. (miltenyibiotec.com)
  • whereas
  • Tyrosine kinase receptor expression on putative hemopoietic stem cells (HSC) 2 shows a reciprocal pattern, with mouse HSC being predominantly c- kit high , flt-3 − , whereas human HSC are predominantly c- kit low , flt-3 + ( 11 ). (jimmunol.org)
  • Surprisingly, however, the mouse contains no group 1 CD1 genes but has two group 2 CD1d genes, whereas the rat contains only one CD1d, and other rodents and mammals may contain 8-12 group 1 CD1 genes. (jimmunol.org)
  • therapies
  • As therapies for human diseases become ever more sophisticated and specifically targeted, it becomes increasingly important to understand the potential limitations of extrapolating data from mice to humans. (jimmunol.org)
  • The literature is littered with examples of therapies that work well in mice but fail to provide similar efficacy in humans ( 2 , 3 , 4 , 5 , 6 , 7 ). (jimmunol.org)