Human lymphocyte cell cycle: Studies with the use of BrUdR

Maur, P. Auf der; Berlincourt-Böhni, Kristina

doi:10.1007/bf00277644

Cited by 24 publications

(5 citation statements)

References 14 publications

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“…On average, only 50% of the original T lymphocytes — indicated by the precursor frequency — responded to the PHA stimulus, with some proliferative responses being as low as ~ 37%. This is in contrast to previous reports dating from the late 1970s, where a proliferative response to PHA stimulus was reported for more than 80% of the cells 3 , 4 . However, the methodologies used in previous reports did not take into account the continuous proliferation of the cells, and thus the exponentially expanding population.…”

Section: Discussioncontrasting

confidence: 99%

“…However, to present day, the available information remains quite conflicting. Various studies described different total cell cycle durations, ranging from 10 to 24 h. Significant variations were particularly reported for the G1 cell cycle phase 1 – 4 , 6 . These discrepancies may be explained by differences in culture methods, mitogen stimuli (often phytohaemagglutinin (PHA)), or even the employed proliferation assays.…”

Section: Introductionmentioning

confidence: 99%

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An updated view into the cell cycle kinetics of human T lymphocytes and the impact of irradiation

Vral

Baeyens

2022

Sci Rep

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Even though a detailed understanding of the proliferative characteristics of T lymphocytes is imperative in many research fields, prior studies have never reached a consensus on these characteristics, and on the corresponding cell cycle kinetics specifically. In this study, the general proliferative response of human T lymphocytes to phytohaemagglutinin (PHA) stimulation was characterized using a carboxyfluorescein succinimidyl ester-based flow cytometric assay. We were able to determine when PHA-stimulated T lymphocytes complete their first division, the proportion of cells that initiate proliferation, the subsequent division rate of the cells, and the impact of irradiation on these proliferative properties. Next, we accurately visualized the cell cycle progression of dividing T lymphocytes cultured in whole blood using an adapted 5-ethynyl-2’-deoxyuridine pulse-chase method. Furthermore, through multiple downstream analysis methods, we were able to make an estimation of the corresponding cell cycle kinetics. We also visualized the impact of X-rays on the progression of the cells through the cell cycle. Our results showed dose-dependent G2 arrest after exposure to irradiation, and a corresponding delay in G1 phase-entry of the cells. In conclusion, utilizing various flow cytometric assays, we provided valuable information on T lymphocyte proliferation characteristics starting from first division to fully dividing cells.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An updated view into the cell cycle kinetics of human T lymphocytes and the impact of irradiation

Vral

Baeyens

2022

Sci Rep

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“…However, direct measurements showed negligible cell proliferation occurred under our culture conditions (Figure S2). Even if some cells did proliferate during culture, resulting in daughter cells sharing the same clonotypes, the length of the cell cycle in human lymphocytes (10–15 hrs) (52) would have precluded more than a single cell division during the culture period. At most, in vitro proliferation could account for no more than 2 daughter cells sharing the same clonotype in an experiment.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals Expanded Clones of Islet Antigen-Reactive CD4+ T Cells in Peripheral Blood of Subjects with Type 1 Diabetes

Cerosaletti¹,

Barahmand-pour-Whitman²,

Yang³

et al. 2017

The Journal of Immunology

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The significance of islet antigen-reactive T cells found in peripheral blood of type 1 diabetes (T1D) subjects is unclear, partly because similar cells are also found in healthy control (HC) subjects. We hypothesized that key disease-associated cells would show evidence of prior antigen exposure, inferred from expanded T cell receptor (TCR) clonotypes, and essential phenotypic properties in their transcriptomes. To test this, we developed single-cell RNA sequencing (RNA-seq) procedures for identifying TCR clonotypes and transcript phenotypes in individual T cells. We applied these procedures to analysis of islet- antigen reactive CD4+ memory T cells from the blood of T1D and HC individuals following activation with pooled immunodominant islet peptides. We found extensive TCR clonotype sharing in antigen-activated cells, especially from individual T1D subjects, consistent with in vivo T cell expansion during disease progression. The expanded clonotype from one T1D subject was detected at repeat visits spanning more than 15 months, demonstrating clonotype stability. Notably, we found no clonotype sharing between subjects, indicating a predominance of “private” TCR specificities. Expanded clones from two T1D subjects recognized distinct IGRP peptides, implicating this molecule as a trigger for CD4+ T cell expansion. While overall transcript profiles of cells from HC and T1D subjects were similar, profiles from the most expanded clones were distinctive. Our findings demonstrate that islet- antigen reactive CD4+ memory T cells with unique antigen specificities and phenotypes are expanded during disease progression and can be detected by single-cell analysis of peripheral blood.

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“…The high turnover condition had a death rate of 0.02/h for all cell types (twice the default), division rates of 0.07/h for the doubly sensitive cells, 0.05/h for the singly resistant cells, and 0.03/h for the doubly resistant cells. The doubling times in Table 2 were within the range of observed human cell division times, namely, from lymphocytes that can divide in less than 10 h [ 62 , 63 , 64 ], to common cancer cell lines in culture that range from 17 to 80 h doubling times [ 65 ].…”

Section: Resultsmentioning

confidence: 88%

In Silico Investigations of Multi-Drug Adaptive Therapy Protocols

Thomas

Cisneros

Anderson

et al. 2022

Cancers

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The standard of care for cancer patients aims to eradicate the tumor by killing the maximum number of cancer cells using the maximum tolerated dose (MTD) of a drug. MTD causes significant toxicity and selects for resistant cells, eventually making the tumor refractory to treatment. Adaptive therapy aims to maximize time to progression (TTP), by maintaining sensitive cells to compete with resistant cells. We explored both dose modulation (DM) protocols and fixed dose (FD) interspersed with drug holiday protocols. In contrast to previous single drug protocols, we explored the determinants of success of two-drug adaptive therapy protocols, using an agent-based model. In almost all cases, DM protocols (but not FD protocols) increased TTP relative to MTD. DM protocols worked well when there was more competition, with a higher cost of resistance, greater cell turnover, and when crowded proliferating cells could replace their neighbors. The amount that the drug dose was changed, mattered less. The more sensitive the protocol was to tumor burden changes, the better. In general, protocols that used as little drug as possible, worked best. Preclinical experiments should test these predictions, especially dose modulation protocols, with the goal of generating successful clinical trials for greater cancer control.

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Human lymphocyte cell cycle: Studies with the use of BrUdR

Cited by 24 publications

References 14 publications

An updated view into the cell cycle kinetics of human T lymphocytes and the impact of irradiation

An updated view into the cell cycle kinetics of human T lymphocytes and the impact of irradiation

Single-Cell RNA Sequencing Reveals Expanded Clones of Islet Antigen-Reactive CD4+ T Cells in Peripheral Blood of Subjects with Type 1 Diabetes

In Silico Investigations of Multi-Drug Adaptive Therapy Protocols

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