X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

PE anti-mouse CD3? antibody

RRID:AB_312673

Antibody ID

AB_312673

Target Antigen

CD3epsilon See NCBI gene mouse

Proper Citation

(BioLegend Cat# 100308, RRID:AB_312673)

Clonality

monoclonal antibody

Comments

Applications: FC

Clone ID

Clone 145-2C11

Host Organism

armenian hamster

Ablation of Transcription Factor IRF4 Promotes Transplant Acceptance by Driving Allogenic CD4+ T Cell Dysfunction.

  • Wu J
  • Immunity
  • 2017 Dec 19

Literature context:


Abstract:

CD4+ T cells orchestrate immune responses and destruction of allogeneic organ transplants, but how this process is regulated on a transcriptional level remains unclear. Here, we demonstrated that interferon regulatory factor 4 (IRF4) was a key transcriptional determinant controlling T cell responses during transplantation. IRF4 deletion in mice resulted in progressive establishment of CD4+ T cell dysfunction and long-term allograft survival. Mechanistically, IRF4 repressed PD-1, Helios, and other molecules associated with T cell dysfunction. In the absence of IRF4, chromatin accessibility and binding of Helios at PD-1 cis-regulatory elements were increased, resulting in enhanced PD-1 expression and CD4+ T cell dysfunction. The dysfunctional state of Irf4-deficient T cells was initially reversible by PD-1 ligand blockade, but it progressively developed into an irreversible state. Hence, IRF4 controls a core regulatory circuit of CD4+ T cell dysfunction, and targeting IRF4 represents a potential therapeutic strategy for achieving transplant acceptance.

Funding information:
  • Biotechnology and Biological Sciences Research Council - (United Kingdom)
  • NIAID NIH HHS - R01 AI106200()

The DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor-Infiltrating Myeloid Cells to Promote Melanoma Progression.

  • Pan W
  • Immunity
  • 2017 Aug 15

Literature context:


Abstract:

Ten-Eleven-Translocation-2 (Tet2) is a DNA methylcytosine dioxygenase that functions as a tumor suppressor in hematopoietic malignancies. We examined the role of Tet2 in tumor-tissue myeloid cells and found that Tet2 sustains the immunosuppressive function of these cells. We found that Tet2 expression is increased in intratumoral myeloid cells both in mouse models of melanoma and in melanoma patients and that this increased expression is dependent on an IL-1R-MyD88 pathway. Ablation of Tet2 in myeloid cells suppressed melanoma growth in vivo and shifted the immunosuppressive gene expression program in tumor-associated macrophages to a proinflammatory one, with a concomitant reduction of the immunosuppressive function. This resulted in increased numbers of effector T cells in the tumor, and T cell depletion abolished the reduced tumor growth observed upon myeloid-specific deletion of Tet2. Our findings reveal a non-cell-intrinsic, tumor-promoting function for Tet2 and suggest that Tet2 may present a therapeutic target for the treatment of non-hematologic malignancies.

Funding information:
  • NCI NIH HHS - R01 CA149109()

A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment.

  • Sierro F
  • Immunity
  • 2017 Aug 15

Literature context:


Abstract:

The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver.

Funding information:
  • NIMH NIH HHS - DP2 MH104119(United States)

Mice deficient of Myc super-enhancer region reveal differential control mechanism between normal and pathological growth.

  • Dave K
  • Elife
  • 2017 Jun 6

Literature context:


Abstract:

The gene desert upstream of the MYC oncogene on chromosome 8q24 contains susceptibility loci for several major forms of human cancer. The region shows high conservation between human and mouse and contains multiple MYC enhancers that are activated in tumor cells. However, the role of this region in normal development has not been addressed. Here we show that a 538 kb deletion of the entire MYC upstream super-enhancer region in mice results in 50% to 80% decrease in Myc expression in multiple tissues. The mice are viable and show no overt phenotype. However, they are resistant to tumorigenesis, and most normal cells isolated from them grow slowly in culture. These results reveal that only cells whose MYC activity is increased by serum or oncogenic driver mutations depend on the 8q24 super-enhancer region, and indicate that targeting the activity of this element is a promising strategy of cancer chemoprevention and therapy.

Long-term intravital imaging of the multicolor-coded tumor microenvironment during combination immunotherapy.

  • Qi S
  • Elife
  • 2016 Nov 18

Literature context:


Abstract:

The combined-immunotherapy of adoptive cell therapy (ACT) and cyclophosphamide (CTX) is one of the most efficient treatments for melanoma patients. However, no synergistic effects of CTX and ACT on the spatio-temporal dynamics of immunocytes in vivo have been described. Here, we visualized key cell events in immunotherapy-elicited immunoreactions in a multicolor-coded tumor microenvironment, and then established an optimal strategy of metronomic combined-immunotherapy to enhance anti-tumor efficacy. Intravital imaging data indicated that regulatory T cells formed an 'immunosuppressive ring' around a solid tumor. The CTX-ACT combined-treatment elicited synergistic immunoreactions in tumor areas, which included relieving the immune suppression, triggering the transient activation of endogenous tumor-infiltrating immunocytes, increasing the accumulation of adoptive cytotoxic T lymphocytes, and accelerating the infiltration of dendritic cells. These insights into the spatio-temporal dynamics of immunocytes are beneficial for optimizing immunotherapy and provide new approaches for elucidating the mechanisms underlying the involvement of immunocytes in cancer immunotherapy.

Funding information:
  • NIH HHS - P51 OD011133(United States)

A postnatal peak in microglial development in the mouse hippocampus is correlated with heightened sensitivity to seizure triggers.

  • Kim I
  • Brain Behav
  • 2015 Dec 25

Literature context:


Abstract:

BACKGROUND: Explosive synaptogenesis and synaptic pruning occur in the hippocampus during the first two weeks of postnatal life, coincident with a heightened susceptibility to seizures in rodents. To determine the temporal correlation between microglial development and age-dependent susceptibility and response to seizures, we quantified developmental changes in basal microglia levels and seizure-induced microglial activation in the hippocampus of Cx3Cr1(GFP /+) transgenic mice. METHODS: Basal levels of microglia were quantified in the hippocampi of Cx3Cr1(GFP /+) mice at P0, P5, P10, P15, P20, P25, P30, P40, and P60. Seizure susceptibility and seizure-induced microglial activation were assessed in response to febrile seizures (lipopolysaccharide followed by hyperthermia) and kainic acid-induced status epilepticus. RESULTS: The density of microglia within the hippocampus increased rapidly after birth, reaching a peak during the second week of life - the age at which the animals became most vulnerable to seizure triggers. In addition, this peak of microglial development and seizure vulnerability during the second postnatal week represented the time of maximal seizure-induced microglia activation. CONCLUSIONS: Overreactive innate immunity mediated by activated microglia may exacerbate acute injury to neuronal synapses and contribute to the long-term epileptogenic effects of early-life seizures. Anti-inflammatory therapy targeting excessive production of inflammatory mediators by activated microglia, therefore, may be an effective age-specific therapeutic strategy to minimize neuronal dysfunction and prevent increases in susceptibility to subsequent seizures in developing animals.