scholarly journals A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells

2019 ◽  
Author(s):  
Enas Abu-Shah ◽  
Philippos Demetriou ◽  
Stefan Balint ◽  
Viveka Mayya ◽  
Mikhail A. Kutuzov ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Cell ◽  
Population Based ◽  
Functional Responses ◽  
Human Immunology ◽  
Human T Cells ◽  
Activation Dynamics ◽  
Cd4 Help ◽  
Effect Of Pd

AbstractResearch in the field of human immunology is restricted by the lack of a system that reconstitutes the in-situ activation dynamics of quiescent human antigen-specific T-cells interacting with dendritic cells. Here we report a tissue-like system that recapitulates the dynamics of engineered primary human immune cell. Our approach facilitates real-time single cell manipulations, tracking of interactions and functional responses complemented by population-based measurements of cytokines, activation status and proliferation. As a proof of concept, we recapitulate immunological phenomenon such as CD4 help to CD8 T-cells through enhanced maturation of DCs and effect of PD-1 checkpoint blockades. In addition, we characterise unique dynamics of T-cell/DC interactions as a function of antigen affinity.

scholarly journals A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Enas Abu-Shah ◽  
Philippos Demetriou ◽  
Štefan Bálint ◽  
Viveka Mayya ◽  
Mikhail A Kutuzov ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Cell ◽  
Population Based ◽  
Functional Responses ◽  
Human Immunology ◽  
Human T Cells ◽  
Activation Dynamics ◽  
Effect Of Pd

Research in the field of human immunology is restricted by the lack of a system that reconstitutes the in-situactivation dynamics of quiescent human antigen-specific T-cells interacting with dendritic cells. Here we report a tissue-like system that recapitulates the dynamics of engineered primary human immune cell. Our approach facilitates real-time single-cell manipulations, tracking of interactions and functional responses complemented by population-based measurements of cytokines, activation status and proliferation. As a proof of concept, we recapitulate immunological phenomenon such as CD4 T-cells' help to CD8 T-cells through enhanced maturation of DCs and the effect of PD-1 checkpoint blockades. In addition, we characterise unique dynamics of T-cell/DC interactions as a function of antigen affinity.

Plasmin and regulators of plasmin activity control the migratory capacity and adhesion of human T cells and dendritic cells by regulating cleavage of the chemokine CCL21

2016 ◽  
Vol 94 (10) ◽  
pp. 955-963 ◽  
Author(s):  
Natalie Lorenz ◽  
Evert Jan Loef ◽  
Inken D Kelch ◽  
Daniel J Verdon ◽  
Moyra M Black ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Plasmin Activity ◽  
Migratory Capacity ◽  
Human T Cells

scholarly journals Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Peter A. Szabo ◽  
Hanna Mendes Levitin ◽  
Michelle Miron ◽  
Mark E. Snyder ◽  
Takashi Senda ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interferon Response ◽  
Functional Responses ◽  
Multiple Tumor ◽  
Human T Cell ◽  
Human T Cells

Abstract Human T cells coordinate adaptive immunity in diverse anatomic compartments through production of cytokines and effector molecules, but it is unclear how tissue site influences T cell persistence and function. Here, we use single cell RNA-sequencing (scRNA-seq) to define the heterogeneity of human T cells isolated from lungs, lymph nodes, bone marrow and blood, and their functional responses following stimulation. Through analysis of >50,000 resting and activated T cells, we reveal tissue T cell signatures in mucosal and lymphoid sites, and lineage-specific activation states across all sites including distinct effector states for CD8+ T cells and an interferon-response state for CD4+ T cells. Comparing scRNA-seq profiles of tumor-associated T cells to our dataset reveals predominant activated CD8+ compared to CD4+ T cell states within multiple tumor types. Our results therefore establish a high dimensional reference map of human T cell activation in health for analyzing T cells in disease.

scholarly journals Prognostic Interactions between FAP+ Fibroblasts and CD8a+ T Cells in Colon Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3238
Author(s):  
Mercedes Herrera ◽  
Artur Mezheyeuski ◽  
Lisa Villabona ◽  
Sara Corvigno ◽  
Carina Strell ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Immune Surveillance ◽  
Prognostic Significance ◽  
Experimental Studies ◽  
Population Based ◽  
Good Prognosis ◽  
High Group

Inter-case variations in immune cell and fibroblast composition are associated with prognosis in solid tumors, including colon cancer. A series of experimental studies suggest immune-modulatory roles of marker-defined fibroblast populations, including FAP-positive fibroblasts. These studies imply that the fibroblast status of tumors might affect the prognostic significance of immune-related features. Analyses of a population-based colon cancer cohort demonstrated good prognosis associations of FAP intensity and CD8a density. Notably, a significant prognostic interaction was detected between these markers (p = 0.013 in nonadjusted analyses and p = 0.003 in analyses adjusted for cofounding factors) in a manner where the good prognosis association of CD8 density was restricted to the FAP intensity-high group. This prognostic interaction was also detected in an independent randomized trial-derived colon cancer cohort (p = 0.048 in nonadjusted analyses). In the CD8-high group, FAP intensity was significantly associated with a higher total tumor density of FoxP3-positive immune cells and a higher ratio of epithelial-to-stromal density of CD8a T cells. The study presents findings relevant for the ongoing efforts to improve the prognostic performance of CD8-related markers and should be followed by additional validation studies. Furthermore, findings support, in general, earlier model-derived studies implying fibroblast subsets as clinically relevant modulators of immune surveillance. Finally, the associations between FAP intensity and specific immune features suggest mechanisms of fibroblast-immune crosstalk with therapeutic potential.

scholarly journals Differential Responses to IFN-α Subtypes in Human T Cells and Dendritic Cells

2003 ◽  
Vol 171 (10) ◽  
pp. 5255-5263 ◽  
Author(s):  
Catharien M. U. Hilkens ◽  
Jörg F. Schlaak ◽  
Ian M. Kerr
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Human T Cells ◽  
Differential Responses

scholarly journals Dendritic Cells Induce MUC1 Expression and Polarization on Human T Cells by an IL-7-Dependent Mechanism

2005 ◽  
Vol 174 (4) ◽  
pp. 2376-2386 ◽  
Author(s):  
Baldev Vasir ◽  
David Avigan ◽  
Zekui Wu ◽  
Keith Crawford ◽  
Shawn Turnquist ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Muc1 Expression ◽  
Human T Cells ◽  
Dependent Mechanism

scholarly journals CTS™ immune cell SR for serum free culture and expansion of human T cells

2015 ◽  
Vol 3 (Suppl 2) ◽  
pp. P1
Author(s):  
Grethe Okern ◽  
Angel Varela-Rohena ◽  
Sandra Kuligowski ◽  
Brian Newsom ◽  
Tanja Aarvak
Keyword(s):  
T Cells ◽  
Immune Cell ◽  
Serum Free ◽  
Human T Cells
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