scholarly journals Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector function

Blood ◽  
2010 ◽  
Vol 115 (17) ◽  
pp. 3498-3507 ◽  
Author(s):  
Vanessa Morales-Tirado ◽  
Dorothy K. Sojka ◽  
Shoshana D. Katzman ◽  
Christopher A. Lazarski ◽  
Fred D. Finkelman ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Actin Polymerization ◽  
Leishmania Major ◽  
Immune Cell ◽  
Effector Function ◽  
Dominant Negative ◽  
Nippostrongylus Brasiliensis ◽  
Wiskott Aldrich Syndrome ◽  
Gata3 Mrna

Abstract Patients with Wiskott-Aldrich syndrome (WAS) have numerous immune cell deficiencies, but it remains unclear how abnormalities in individual cell types contribute to the pathologies of WAS. In T cells, the WAS protein (WASp) regulates actin polymerization and transcription, and plays a role in the dynamics of the immunologic synapse. To examine how these events influence CD4 function, we isolated the WASp deficiency to CD4+ T cells by adoptive transfer into wild-type mice to study T-cell priming and effector function. WAS−/− CD4+ T cells mediated protective T-helper 1 (Th1) responses to Leishmania major in vivo, but were unable to support Th2 immunity to Nippostrongylus brasiliensis or L major. Mechanistically, WASp was not required for Th2 programming but was required for Th2 effector function. WAS−/− CD4+ T cells up-regulated IL-4 and GATA3 mRNA and secreted IL-4 protein during Th2 differentiation. In contrast, cytokine transcription was uncoupled from protein production in WAS−/− Th2-primed effectors. WAS−/− Th2s failed to produce IL-4 protein on restimulation despite elevated IL-4/GATA3 mRNA. Moreover, dominant-negative WASp expression in WT effector T cells blocked IL-4 production, but had no effect on IFNγ. Thus WASp plays a selective, posttranscriptional role in Th2 effector function.

823 CD4 T cells are essential for an anti-tumor effect in a B78 murine melanoma tumor model

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A873-A873
Author(s):  
Arika Feils ◽  
Mackenzie Heck ◽  
Anna Hoefges ◽  
Peter Carlson ◽  
Luke Zangl ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Cd4 T Cells ◽  
Tumor Response ◽  
Immune Cell ◽  
Cd8 T Cell ◽  
Mhc I ◽  
Mhc Ii ◽  
Flow Cytometric

BackgroundMice bearing B78 melanoma tumors can be cured using an in situ vaccine (ISV) regimen that includes radiation (RT) together with immunocytokine (tumor-targeting mAb conjugated to IL-2). B78 melanoma cells, derived from B16 cells, express minimal to no MHC-I but express MHC-II upon IFN-g/TNF-a stimulation. Although B78 cells are primarily MHC-I-deficient, an increased CD8 T cell infiltration into the tumor microenvironment (TME) has been shown following ISV.1 To further investigate the potential role of specific immune cell lineages in the B78 anti-tumor response to ISV, immune subset depletion studies and flow cytometric analyses were performed.MethodsC57BL/6 mice bearing B78 tumors were depleted of immune cell subsets with mAbs (anti-CD4, anti-CD8, anti-NK1.1, or Rat IgG control) for 3 weeks during the course of treatment. Treatment groups included no treatment, RT (12 Gy), or ISV (RT D0 and immunocytokine D5-D9). 6 mice/group (repeated three times) were followed for survival/tumor growth, and flow cytometry studies included 4 mice/group, sacrificed on D8 and D13 following the start of ISV.ResultsMice depleted of CD4 T cells during the course of ISV showed a significant reduction of anti-tumor effect as compared to mice treated with ISV/Rat IgG (pConclusionsThese studies suggest that CD4 T cells are essential for an anti-tumor response in the B78 melanoma model. In vivo depletion data show that CD4 T cells, but not CD8 or NK cells, are required for a decrease in tumor growth via ISV. Flow cytometric analyses suggest an interplay between CD4 and CD8 T cells as indicated by a decrease in CD8/IFN-g expression following ISV in the absence of CD4 T cells. The role that MHC-I and MHC-II expression plays in this CD4/CD8 T cell anti-tumor response is under investigation. In future studies, B78 melanoma may serve as a critical syngeneic model for development of more effective immunotherapy treatment regimens.Ethics ApprovalAll animal experiments were performed in accordance with protocols approved by Animal Care and Use Committees of the University of Wisconsin-Madison.ReferenceMorris Z, Guy E, Francis D, et al. In situ tumor vaccination by combining local radiation and tumor-specific antibody or immunocytokine treatments. Cancer Res 2016;76(13):3929-3941.

scholarly journals Immune classification of clear cell renal cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sumeyye Su ◽  
Shaya Akbarinejad ◽  
Leili Shahriyari
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Renal Cell ◽  
Cd4 T Cells ◽  
Immune Cell ◽  
Clear Cell ◽  
P Value ◽  
Cell Type ◽  
Primary Tumors ◽  
Immune Cell Type

AbstractSince the outcome of treatments, particularly immunotherapeutic interventions, depends on the tumor immune micro-environment (TIM), several experimental and computational tools such as flow cytometry, immunohistochemistry, and digital cytometry have been developed and utilized to classify TIM variations. In this project, we identify immune pattern of clear cell renal cell carcinomas (ccRCC) by estimating the percentage of each immune cell type in 526 renal tumors using the new powerful technique of digital cytometry. The results, which are in agreement with the results of a large-scale mass cytometry analysis, show that the most frequent immune cell types in ccRCC tumors are CD8+ T-cells, macrophages, and CD4+ T-cells. Saliently, unsupervised clustering of ccRCC primary tumors based on their relative number of immune cells indicates the existence of four distinct groups of ccRCC tumors. Tumors in the first group consist of approximately the same numbers of macrophages and CD8+ T-cells and and a slightly smaller number of CD4+ T cells than CD8+ T cells, while tumors in the second group have a significantly high number of macrophages compared to any other immune cell type (P-value $$<0.01$$ < 0.01 ). The third group of ccRCC tumors have a significantly higher number of CD8+ T-cells than any other immune cell type (P-value $$<0.01$$ < 0.01 ), while tumors in the group 4 have approximately the same numbers of macrophages and CD4+ T-cells and a significantly smaller number of CD8+ T-cells than CD4+ T-cells (P-value $$<0.01$$ < 0.01 ). Moreover, there is a high positive correlation between the expression levels of IFNG and PDCD1 and the percentage of CD8+ T-cells, and higher stage and grade of tumors have a substantially higher percentage of CD8+ T-cells. Furthermore, the primary tumors of patients, who are tumor free at the last time of follow up, have a significantly higher percentage of mast cells (P-value $$<0.01$$ < 0.01 ) compared to the patients with tumors for all groups of tumors except group 3.

scholarly journals Runx proteins regulate Foxp3 expression

2009 ◽  
Vol 206 (11) ◽  
pp. 2329-2337 ◽  
Author(s):  
Ludovica Bruno ◽  
Luca Mazzarella ◽  
Maarten Hoogenkamp ◽  
Arnulf Hertweck ◽  
Bradley S. Cobb ◽  
...  
Keyword(s):  
T Cells ◽  
Dna Binding ◽  
Cd4 T Cells ◽  
Target Genes ◽  
De Novo ◽  
Foxp3 Expression ◽  
Regulatory Elements ◽  
Dominant Negative ◽  
Downstream Target ◽  
Runx Proteins

Runx proteins are essential for hematopoiesis and play an important role in T cell development by regulating key target genes, such as CD4 and CD8 as well as lymphokine genes, during the specialization of naive CD4 T cells into distinct T helper subsets. In regulatory T (T reg) cells, the signature transcription factor Foxp3 interacts with and modulates the function of several other DNA binding proteins, including Runx family members, at the protein level. We show that Runx proteins also regulate the initiation and the maintenance of Foxp3 gene expression in CD4 T cells. Full-length Runx promoted the de novo expression of Foxp3 during inducible T reg cell differentiation, whereas the isolated dominant-negative Runt DNA binding domain antagonized de novo Foxp3 expression. Foxp3 expression in natural T reg cells remained dependent on Runx proteins and correlated with the binding of Runx/core-binding factor β to regulatory elements within the Foxp3 locus. Our data show that Runx and Foxp3 are components of a feed-forward loop in which Runx proteins contribute to the expression of Foxp3 and cooperate with Foxp3 proteins to regulate the expression of downstream target genes.

scholarly journals IL-4 Rapidly Produced by Vβ4 Vα8 CD4+ T Cells Instructs Th2 Development and Susceptibility to Leishmania major in BALB/c Mice

Immunity ◽  
1997 ◽  
Vol 6 (5) ◽  
pp. 541-549 ◽  
Author(s):  
Pascal Launois ◽  
Ivan Maillard ◽  
Sabine Pingel ◽  
Kristin G. Swihart ◽  
Ioannis Xénarios ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Leishmania Major ◽  
Th2 Development

Blockade of CD40 Signaling on Diabetogenic CD4 T Cells Inhibits Effector Function

2010 ◽  
Vol 135 ◽  
pp. S132
Author(s):  
Rocky Baker ◽  
Thierry Mallevaey ◽  
Laurent Gapin ◽  
Kathrin Haskins
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Effector Function

Resveratrol stimulates the metabolic reprogramming of human CD4+T cells to enhance effector function

2017 ◽  
Vol 10 (501) ◽  
pp. eaal3024 ◽  
Author(s):  
Marco Craveiro ◽  
Gaspard Cretenet ◽  
Cédric Mongellaz ◽  
Maria I. Matias ◽  
Olivier Caron ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Effector Function ◽  
Metabolic Reprogramming

scholarly journals Borna disease, a progressive meningoencephalomyelitis as a model for CD4+ T cell-mediated immunopathology in the brain.

1989 ◽  
Vol 170 (3) ◽  
pp. 1045-1050 ◽  
Author(s):  
J A Richt ◽  
L Stitz ◽  
H Wekerle ◽  
R Rott
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Line ◽  
Mhc Class Ii ◽  
Adoptive Transfer ◽  
Cd4 T Cells ◽  
Immune Cell ◽  
Cd4 T Cell ◽  
The Brain ◽  
Borna Disease

A homogeneous T cell line NM1 with Borna disease (BD) virus reactivity could be established. The NM1 cells have been characterized as CD4+ T cells. Adoptive transfer revealed that this MHC class II-restricted immune cell is responsible for the immunopathological effect leading to BD, a progressive meningoencephalomyelitis.

scholarly journals Disparate Primary and Secondary Allospecific CD8+ T Cell Cytolytic Effector Function in the Presence or Absence of Host CD4+ T Cells

2007 ◽  
Vol 179 (1) ◽  
pp. 80-88 ◽  
Author(s):  
Phillip H. Horne ◽  
Mitchel A. Koester ◽  
Kartika Jayashankar ◽  
Keri E. Lunsford ◽  
Heather L. Dziema ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
Effector Function
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