scholarly journals High-density preculture of PBMCs restores defective sensitivity of circulating CD8 T cells to virus- and tumor-derived antigens

Blood ◽  
2015 ◽  
Vol 126 (2) ◽  
pp. 185-194 ◽  
Author(s):  
Julia Wegner ◽  
Stephan Hackenberg ◽  
Claus-Jürgen Scholz ◽  
Sergey Chuvpilo ◽  
Dmitry Tyrsin ◽  
...  

Key Points CD8 memory T cells in PBMCs are antigen-hyporesponsive due to loss of priming by tissue-dependent interactions. Preculture at high cell density allows the detection of antiviral and antitumor responses that may be overlooked without this step.

Blood ◽  
2013 ◽  
Vol 122 (3) ◽  
pp. 405-412 ◽  
Author(s):  
Marco Frentsch ◽  
Regina Stark ◽  
Nadine Matzmohr ◽  
Sarah Meier ◽  
Sibel Durlanik ◽  
...  

Key Points A major part of CD8+ memory T cells expresses CD40L, the key molecule for T-cell–dependent help. CD40L-expressing CD8+ T cells resemble functional CD4+ helper T cells.


Blood ◽  
2014 ◽  
Vol 124 (4) ◽  
pp. 628-637 ◽  
Author(s):  
Christian Stemberger ◽  
Patricia Graef ◽  
Marcus Odendahl ◽  
Julia Albrecht ◽  
Georg Dössinger ◽  
...  

Key Points Lowest numbers of ex vivo–selected CD8+ memory T cells can reconstitute pathogen-specific immunity in immunocompromised hosts.


2020 ◽  
Author(s):  
Michael Caplow

AbstractYeast secrete ATP in response to glucose, a property with previously unknown functional consequence. In this report, we show that extracellular ATP is a signal for growth of surrounding cells. The ATP signaling behavior was uncovered by finding reduced toxicity of an inducible, dominant-lethal form of alpha tubulin (tub1-828) in cells grown at high, compared to low cell density. Reduced cell death at high cell density resulted because the rate of chromosome loss/cell division was lower (18-fold) in a cultures inoculated with a high density (350,000) compared to a low density (5,000) of cells. The sparing effect of growth at high cell density could be replicated by growing together 3440 cells that express tub1-828, with 2.3 E6 cells that do not express the mutant protein. Toxicity was reduced at high cell density apparently because a secreted signal induces growth, so that the mutant protein is rapidly diluted by synthesis of wild-type α-tubulin. Further, fluorescence-activated cell sorting (FACS) analysis after DNA staining showed that the rate of the G1-G2 transition was faster with cells at high density. ATP replaced the need for high cell density for resistance to tub1-828, and stimulated the transition from G1 to G2 in cells at low density. Cells lacking the enzyme nucleoside diphosphate kinase did not respond to nucleotide stimulation of growth during expression of mutant tubulin, suggesting that NDP kinase has a regulatory role in growth stimulation. This newly discovered quorum sensing response in yeast, mediated by ATP, indicates that yeast decision-making is not entirely autonomous.


2018 ◽  
Vol 2 (6) ◽  
pp. 681-690 ◽  
Author(s):  
Lori Muffly ◽  
Kevin Sheehan ◽  
Randall Armstrong ◽  
Kent Jensen ◽  
Keri Tate ◽  
...  

Key Points Phenotypic TM isolation from unmanipulated donor apheresis via CD45RA depletion followed by CD8+ enrichment is feasible. TM infusion for patients with relapse after allogeneic HCT was safe and resulted in minimal GVHD.


Bioprinting ◽  
2021 ◽  
pp. 202-218
Author(s):  
Kenneth Douglas

Abstract: This chapter attempts to peer into the possible future of bioprinting to consider two conceivable directions that bioprinting might take while also contemplating what we may be able to learn about bioprinting’s trajectory by reflecting on another biomedical quest—the twentieth-century’s attempt to conquer polio. In one study that might offer a route for bioprinting, a team created bioconstructs with cell densities approaching that of native tissue (about 108 cells/gram). The group used embedded 3D printing to create a branched, hierarchical network of vascular channels within a large, high cell density bioconstruct and perfused media through the channels that they created using fugitive ink. This was to provide nutrient support for the cells. They also built a high-density cardiac construct in which the cells beat synchronously and showed functional contractility. They quantitatively measured the deformation of the cardiac tissue during contraction.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Remy Colin ◽  
Knut Drescher ◽  
Victor Sourjik

AbstractAt high cell density, swimming bacteria exhibit collective motility patterns, self-organized through physical interactions of a however still debated nature. Although high-density behaviours are frequent in natural situations, it remained unknown how collective motion affects chemotaxis, the main physiological function of motility, which enables bacteria to follow environmental gradients in their habitats. Here, we systematically investigate this question in the model organism Escherichia coli, varying cell density, cell length, and suspension confinement. The characteristics of the collective motion indicate that hydrodynamic interactions between swimmers made the primary contribution to its emergence. We observe that the chemotactic drift is moderately enhanced at intermediate cell densities, peaks, and is then strongly suppressed at higher densities. Numerical simulations reveal that this suppression occurs because the collective motion disturbs the choreography necessary for chemotactic sensing. We suggest that this physical hindrance imposes a fundamental constraint on high-density behaviours of motile bacteria, including swarming and the formation of multicellular aggregates and biofilms.


2015 ◽  
Vol 15 (4) ◽  
pp. 357-367 ◽  
Author(s):  
Melanie Werner ◽  
Daria Schmoldt ◽  
Frank Hilbrig ◽  
Valérie Jérôme ◽  
Alexander Raup ◽  
...  

2002 ◽  
Vol 195 (12) ◽  
pp. 1515-1522 ◽  
Author(s):  
Ananda W. Goldrath ◽  
Pallavur V. Sivakumar ◽  
Moira Glaccum ◽  
Mary K. Kennedy ◽  
Michael J. Bevan ◽  
...  

Both naive and memory T cells undergo antigen-independent proliferation after transfer into a T cell–depleted environment (acute homeostatic proliferation), whereas only memory T cells slowly divide in a full T cell compartment (basal proliferation). We show, first, that naive and memory CD8+ T cells have different cytokine requirements for acute homeostatic proliferation. Interleukin (IL)-7 receptor(R)α–mediated signals were obligatory for proliferation of naive T cells in lymphopenic hosts, whereas IL-15 did not influence their division. Memory T cells, on the other hand, could use either IL-7Rα– or IL-15–mediated signals for acute homeostatic proliferation: their proliferation was delayed when either IL-7Rα was blocked or IL-15 removed, but only when both signals were absent was proliferation ablated. Second, the cytokine requirements for basal and acute homeostatic proliferation of CD8+ memory T cells differ, as basal division of memory T cells was blocked completely in IL-15–deficient hosts. These data suggest a possible mechanism for the dearth of memory CD8+ T cells in IL-15– and IL-15Rα–deficient mice is their impaired basal proliferation. Our results show that naive and memory T lymphocytes differ in their cytokine dependence for acute homeostatic proliferation and that memory T lymphocytes have distinct requirements for proliferation in full versus empty compartments.


2018 ◽  
Author(s):  
Remy Colin ◽  
Knut Drescher ◽  
Victor Sourjik

AbstractAt high cell density, swimming bacteria exhibit collective motility patterns, self-organized through physical interactions of a however still debated nature. Although high-density behaviours are frequent in natural situations, it remained unknown how collective motion affects chemotaxis, the main physiological function of motility, which enables bacteria to follow environmental gradients in their habitats. Here, we systematically investigate this question in the model organismEscherichia coli, varying cell density, cell length, and suspension confinement. The characteristics of the collective motion indicate that hydrodynamic interactions between swimmers made the primary contribution to its emergence. We observe that the chemotactic drift is moderately enhanced at intermediate cell densities, peaks, and is then strongly suppressed at higher densities. Numerical simulations reveal that this suppression occurs because the collective motion disturbs the choreography necessary for chemotactic sensing. We suggest that this physical hindrance imposes a fundamental constraint on high-density behaviours of motile bacteria, including swarming and the formation of multicellular aggregates and biofilms.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Hana A Itani ◽  
Feng Zhang ◽  
Liang Xiao ◽  
Wei Chen ◽  
David G Harrison

Immunological memory is an important component of the adaptive immune response to pathogenic stimuli. Effector memory T cells, which are CD44high CD62Llow, reside in various non-lymphoid tissues and serve as a first line defense against foreign antigens. We have previously shown that T cells are important in hypertension, but the role of memory T cells has not been defined. Thus we hypothesized that CD8+ memory T cells are component of this memory response. To test this hypothesis, mice initially received two weeks of ang II, were allowed to recover for 3 weeks and were then re-infused with low dose of ang II (140 ng/kg/min) that minimally raises blood pressure in naïve mice. This low-dose of ang II increased blood pressure to 137±6 mmHg in mice that had previously received a vehicle infusion, but to 172±12 mmHg in mice that had received ang II. In keeping with a memory T cell response, we found that angiotensin II causes a 5 to 10-fold increase in CD8+ CD62Lhigh/CD44high/CCR7+ central memory cells in the kidney while reducing these effector memory CD8+ T cells in the spleen. CD8+ memory T cells require co-stimulatory signaling between CD70 on macrophages and CD27 on T cells. We found that angiotensin II infusion increased CD70 mRNA in isolated kidney vessels by 5 to 10-fold. Similarly, flow cytometry revealed that angiotensin II increased macrophages expressing CD70 and CD8+ T cells expressing CD27 expression in the kidney. Thus, these studies indicate that repeated exposures to angiotensin II promote an immune memory response of CD8+ T cells and markedly enhance the hypertensive response to this octapeptide. The role of CD27 and CD70 signaling requires additional study but might serve as a therapeutic target.


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