Artificial Methods for T Cell Activation: Critical Tools in T Cell Biology and T Cell Immunotherapy

2018 ◽  
pp. 207-219 ◽  
Author(s):  
Kyung-Ho Roh
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Biology ◽  
Cell Activation ◽  
Cell Immunotherapy ◽  
T Cell Biology ◽  
T Cell Immunotherapy

scholarly journals Computational properties of mitochondria in T cell activation and fate

Open Biology ◽  
2016 ◽  
Vol 6 (11) ◽  
pp. 160192 ◽  
Author(s):  
Roman Uzhachenko ◽  
Anil Shanker ◽  
Geneviève Dupont
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Biology ◽  
Pid Controller ◽  
Cell Activation ◽  
Digital Signal ◽  
Cell Life ◽  
T Cell Biology ◽  
Cellular Ca ◽  
Computational Properties

In this article, we review how mitochondrial Ca 2+ transport (mitochondrial Ca 2+ uptake and Na + /Ca 2+ exchange) is involved in T cell biology, including activation and differentiation through shaping cellular Ca 2+ signals. Based on recent observations, we propose that the Ca 2+ crosstalk between mitochondria, endoplasmic reticulum and cytoplasm may form a proportional–integral–derivative (PID) controller. This PID mechanism (which is well known in engineering) could be responsible for computing cellular decisions. In addition, we point out the importance of analogue and digital signal processing in T cell life and implication of mitochondrial Ca 2+ transport in this process.

scholarly journals The chaperonin CCT8 controls proteostasis essential for T cell maturation, selection, and function

2020 ◽  
Author(s):  
Bergithe E Oftedal ◽  
Stefano Maio ◽  
Adam Handel ◽  
Madeleine PJ White ◽  
Duncan Howie ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Biology ◽  
Cell Activation ◽  
T Cell Biology ◽  
Th2 Polarization ◽  
Cell Stress Response ◽  
And Function ◽  
Induced Changes

AbstractT cells rely for their development and function on the correct folding and turnover of proteins generated in response to a broad range of molecular cues. In the absence of the eukaryotic type II chaperonin complex, CCT, T cell activation induced changes in the proteome are compromised including the formation of nuclear actin filaments and the formation of a normal cell stress response. Consequently, thymocyte maturation and selection, and T cell homeostatic maintenance and receptor-mediated activation are severely impaired. Additionally, Th2 polarization digresses in the absence of CCT-controlled protein folding resulting paradoxically in continued IFN-γ expression. As a result, CCT-deficient T cells fail to generate an efficient immune protection against helminths as they are unable to sustain a coordinated recruitment of the innate and adaptive immune systems. These findings thus demonstrate that normal T cell biology is critically dependent on CCT-controlled proteostasis and that its absence is incompatible with protective immunity.

Cell Biology of T Cell Activation and Differentiation

2006 ◽  
pp. 217-274 ◽  
Author(s):  
María Angélica Santana ◽  
Fernando Esquivel‐Guadarrama
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Biology ◽  
Cell Activation

scholarly journals Yap suppresses T cell function and infiltration in the tumor microenvironment

2019 ◽  
Author(s):  
Eleni Stampouloglou ◽  
Anthony Federico ◽  
Emily Slaby ◽  
Stefano Monti ◽  
Gregory L. Szeto ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
T Cell Activation ◽  
Cell Biology ◽  
Cell Activation ◽  
Cell Function ◽  
T Cell Responses ◽  
Negative Regulator ◽  
Cell Responses

ABSTRACTA major challenge for cancer immunotherapy is sustaining T cell activation and recruitment in immunosuppressive solid tumors. Here we report that Yap levels are sharply induced upon activation of CD4+ and CD8+ T cells and that Yap functions as an immunosuppressive factor and inhibitor of effector differentiation. Loss of Yap in T cells results in enhanced T cell activation, differentiation and function, which translates in vivo to an improved ability for T cells to infiltrate and repress tumors. Gene expression analyses of tumor-infiltrating T cells following Yap deletion implicates Yap as a mediator of global T cell responses in the tumor microenvironment and as a key negative regulator of T cell tumor infiltration and patient survival in diverse human cancers. Collectively, our results indicate that Yap plays critical roles in T cell biology, and suggest that inhibiting Yap activity improves T cell responses in cancer.

scholarly journals Tumors Exploit Dedicated Intracellular Vesicles to Program T cell Responses

2019 ◽  
Author(s):  
Edward W. Roberts ◽  
Megan K. Ruhland ◽  
En Cai ◽  
Adriana M. Mujal ◽  
Kyle Marchuk ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Biology ◽  
Cell Activation ◽  
Light Sheet ◽  
Multiphoton Imaging ◽  
New Frontier ◽  
Antigen Presenting

AbstractIn order to drive productive tumor-infiltrating lymphocyte (TIL) function, myeloid populations must direct antigens to the lymph node, including to resident antigen-presenting cells (APCs) that have never touched the tumor. It has long been supposed that APCs trade antigens with one another, but the dominant cell biology underlying that remains unknown. We used in vitro and in vivo assays together with lattice light sheet and multiphoton imaging to show that myeloid cells carry tumor antigen-laden vesicles that they ‘trade’ with one another as they reach distant sites. This accounts for the majority of antigen displayed to T cells and provides tumors with a mechanism to access APCs that differentially direct T cell activation away from memory phenotypes. This work defines efficient cell biology that drives the first steps of TIL generation and represents a new frontier for engineering tumoral immunity.

scholarly journals Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity

2020 ◽  
Vol 117 (14) ◽  
pp. 7961-7970 ◽  
Author(s):  
Sandeep Kumar ◽  
Sunil Kumar Singh ◽  
Navin Viswakarma ◽  
Gautam Sondarva ◽  
Rakesh Sathish Nair ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Biology ◽  
Cell Activation ◽  
Nuclear Translocation ◽  
Mixed Lineage Kinase ◽  
Pharmacological Inhibition ◽  
Mixed Lineage Kinase 3

Mixed lineage kinase 3 (MLK3), also known as MAP3K11, was initially identified in a megakaryocytic cell line and is an emerging therapeutic target in cancer, yet its role in immune cells is not known. Here, we report that loss or pharmacological inhibition of MLK3 promotes activation and cytotoxicity of T cells. MLK3 is abundantly expressed in T cells, and its loss alters serum chemokines, cytokines, and CD28 protein expression on T cells and its subsets. MLK3 loss or pharmacological inhibition induces activation of T cells in in vitro, ex vivo, and in vivo conditions, irrespective of T cell activating agents. Conversely, overexpression of MLK3 decreases T cell activation. Mechanistically, loss or inhibition of MLK3 down-regulates expression of a prolyl-isomerase, Ppia, which is directly phosphorylated by MLK3 to increase its isomerase activity. Moreover, MLK3 also phosphorylates nuclear factor of activated T cells 1 (NFATc1) and regulates its nuclear translocation via interaction with Ppia, and this regulates T cell effector function. In an immune-competent mouse model of breast cancer, MLK3 inhibitor increases Granzyme B-positive CD8+T cells and decreases MLK3 and Ppia gene expression in tumor-infiltrating T cells. Likewise, the MLK3 inhibitor in pan T cells, isolated from breast cancer patients, also increases cytotoxic CD8+T cells. These results collectively demonstrate that MLK3 plays an important role in T cell biology, and targeting MLK3 could serve as a potential therapeutic intervention via increasing T cell cytotoxicity in cancer.

scholarly journals Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8+ T cell activation in the presence of adjuvant temozolomide

2018 ◽  
Vol 7 (4) ◽  
pp. e1412901 ◽  
Author(s):  
Serena Pellegatta ◽  
Marica Eoli ◽  
Valeria Cuccarini ◽  
Elena Anghileri ◽  
Bianca Pollo ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Survival Gain ◽  
Adjuvant Temozolomide ◽  
Cell Immunotherapy

Antibody repertoire complexity and effector cell biology determined by assays for IgE-mediated basophil and T-cell activation

2012 ◽  
Vol 383 (1-2) ◽  
pp. 4-20 ◽  
Author(s):  
Gitte Lund ◽  
Nicholas Willumsen ◽  
Jens Holm ◽  
Lars Harder Christensen ◽  
Peter Adler Würtzen ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Biology ◽  
Cell Activation ◽  
Effector Cell ◽  
Antibody Repertoire ◽  
Ige Mediated

scholarly journals Functional proteomic atlas of HIV infection in primary human CD4+ T cells

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Adi Naamati ◽  
James C Williamson ◽  
Edward JD Greenwood ◽  
Sara Marelli ◽  
Paul J Lehner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Biology ◽  
Cell Activation ◽  
Magnetic Beads ◽  
Host Cells ◽  
Dynamic Background

Viruses manipulate host cells to enhance their replication, and the identification of cellular factors targeted by viruses has led to key insights into both viral pathogenesis and cell biology. In this study, we develop an HIV reporter virus (HIV-AFMACS) displaying a streptavidin-binding affinity tag at the surface of infected cells, allowing facile one-step selection with streptavidin-conjugated magnetic beads. We use this system to obtain pure populations of HIV-infected primary human CD4+ T cells for detailed proteomic analysis, and quantitate approximately 9000 proteins across multiple donors on a dynamic background of T cell activation. Amongst 650 HIV-dependent changes (q < 0.05), we describe novel Vif-dependent targets FMR1 and DPH7, and 192 proteins not identified and/or regulated in T cell lines, such as ARID5A and PTPN22. We therefore provide a high-coverage functional proteomic atlas of HIV infection, and a mechanistic account of host factors subverted by the virus in its natural target cell.

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