scholarly journals Functional impairment of CD4 T cells despite normalization of T cell number in HIV

2006 ◽  
Vol 242 (1) ◽  
pp. 46-51 ◽  
Author(s):  
Kenneth S. Knox ◽  
Richard B. Day ◽  
Lisa M. Kohli ◽  
Chadi A. Hage ◽  
Homer L. Twigg
Keyword(s):  
T Cells ◽  
T Cell ◽  
Functional Impairment ◽  
Cd4 T Cells ◽  
Cell Number

scholarly journals Characterisation of CD4+ T-cell subtypes using single cell RNA sequencing and the impact of cell number and sequencing depth

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
James Ding ◽  
Samantha L. Smith ◽  
Gisela Orozco ◽  
Anne Barton ◽  
Steve Eyre ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cd4 T Cells ◽  
Cell Number ◽  
Sequencing Depth ◽  
Cd4 T Cell ◽  
Specific Cell ◽  
The Impact

AbstractCD4+ T-cells represent a heterogeneous collection of specialised sub-types and are a key cell type in the pathogenesis of many diseases due to their role in the adaptive immune system. By investigating CD4+ T-cells at the single cell level, using RNA sequencing (scRNA-seq), there is the potential to identify specific cell states driving disease or treatment response. However, the impact of sequencing depth and cell numbers, two important factors in scRNA-seq, has not been determined for a complex cell population such as CD4+ T-cells. We therefore generated a high depth, high cell number dataset to determine the effect of reduced sequencing depth and cell number on the ability to accurately identify CD4+ T-cell subtypes. Furthermore, we investigated T-cell signatures under resting and stimulated conditions to assess cluster specific effects of stimulation. We found that firstly, cell number has a much more profound effect than sequencing depth on the ability to classify cells; secondly, this effect is greater when cells are unstimulated and finally, resting and stimulated samples can be combined to leverage additional power whilst still allowing differences between samples to be observed. While based on one individual, these results could inform future scRNA-seq studies to ensure the most efficient experimental design.

scholarly journals Limited CD4+ T cell proliferation leads to preservation of CD4+ T cell counts in SIV-infected sooty mangabeys

2010 ◽  
Vol 277 (1701) ◽  
pp. 3773-3781 ◽  
Author(s):  
Ming Liang Chan ◽  
Janka Petravic ◽  
Alexandra M. Ortiz ◽  
Jessica Engram ◽  
Mirko Paiardini ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Number ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Proliferating Cells ◽  
Immunodeficiency Virus ◽  
Sooty Mangabeys

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections result in chronic virus replication and progressive depletion of CD4+ T cells, leading to immunodeficiency and death. In contrast, ‘natural hosts’ of SIV experience persistent infection with high virus replication but no severe CD4+ T cell depletion, and remain AIDS-free. One important difference between pathogenic and non-pathogenic infections is the level of activation and proliferation of CD4+ T cells. We analysed the relationship between CD4+ T cell number and proliferation in HIV, pathogenic SIV in macaques, and non-pathogenic SIV in sooty mangabeys (SMs) and mandrills. We found that CD4+ T cell proliferation was negatively correlated with CD4+ T cell number, suggesting that animals respond to the loss of CD4+ T cells by increasing the proliferation of remaining cells. However, the level of proliferation seen in pathogenic infections (SIV in rhesus macaques and HIV) was much greater than in non-pathogenic infections (SMs and mandrills). We then used a modelling approach to understand how the host proliferative response to CD4+ T cell depletion may impact the outcome of infection. This modelling demonstrates that the rapid proliferation of CD4+ T cells in humans and macaques associated with low CD4+ T cell levels can act to ‘fuel the fire’ of infection by providing more proliferating cells for infection. Natural host species, on the other hand, have limited proliferation of CD4+ T cells at low CD4+ T cell levels, which allows them to restrict the number of proliferating cells susceptible to infection.

scholarly journals Distinctions Between CD8+ and CD4+ T-Cell Regenerative Pathways Result in Prolonged T-Cell Subset Imbalance After Intensive Chemotherapy

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3700-3707 ◽  
Author(s):  
Crystal L. Mackall ◽  
Thomas A. Fleisher ◽  
Margaret R. Brown ◽  
Mary P. Andrich ◽  
Clara C. Chen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Subset ◽  
Cd8 T Cell ◽  
Cell Number ◽  
Cd4 T Cell ◽  
Cell Regeneration ◽  
Intensive Chemotherapy ◽  
T Cell Subset

Rapid recovery of CD4+ T cells after intensive chemotherapy is limited by an age-dependent decline in thymopoiesis. Here we sought to determine whether similar limitations exist for CD8+ T-cell regeneration. After intensive chemotherapy, CD8+ T cells had a faster effective doubling time than CD4+ T cells (median, 12.6 v 28.2 days, P < .05). Accordingly, at 3 months posttherapy, mean CD8+ T-cell number had returned to baseline, whereas mean CD4+ T-cell number was only 35% of pretherapy values (P < .05). These differences were primarily due to very rapid expansion of CD8+CD57+ and CD8+CD28− subsets. At 3 months posttherapy, there was no relationship between age and CD8+ T-cell number (R = −.02), whereas CD4+ T-cell number was inversely related to age (R = −.66) and there were no discernible differences in CD8+ recovery among patients with or without thymic enlargement, whereas CD4+ recovery was enhanced in patients with thymic enlargement after chemotherapy (P < .01). Therefore thymic-independent pathways of T-cell regeneration appear to rapidly regenerate substantial numbers of CD8+, but not CD4+ T cells, resulting in prolonged T-cell subset imbalance after T-cell depletion. These inherent distinctions between CD4+v CD8+ T-cell regeneration may have significant implications for immunotherapeutic strategies undertaken to eradicate minimal residual neoplastic disease after cytoreductive chemotherapy.

Decreased plasma glutamine level and CD4+ T cell number in response to 8 wk of anaerobic training

1997 ◽  
Vol 272 (5) ◽  
pp. E788-E795 ◽  
Author(s):  
V. Hack ◽  
C. Weiss ◽  
B. Friedmann ◽  
S. Suttner ◽  
M. Schykowski ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Absolute Number ◽  
Cell Number ◽  
Cd4 T Cell ◽  
Strong Positive Correlation ◽  
Marked Rise ◽  
Cell Counts ◽  
The Individual

The purpose of the present study was to investigate the role of plasma amino acids and glutathione (GSH) on the absolute number of leukocyte and lymphocyte subpopulations in response to different training programs. Healthy untrained subjects were randomly assigned to an 8-wk aerobic (AET) or anaerobic (ANT) exercise training program. Absolute number of cell counts did not significantly change in AET, whereas a decrease of CD4+ T cell counts (P < 0.05), a fall in cells expressing CD45RA+ antigen (P < 0.05), and a marked increase in CD8+ T cell numbers (P < 0.01) were noted in ANT at the end of the training period compared with baseline values. Furthermore, ANT demonstrated a marked rise (P < 0.001) in plasma glutamate from 27.6 +/- 2.8 to 49.8 +/- 5.2 microM and a considerable reduction (P < 0.001) of the plasma glutamine pool from 713 +/- 22 to 601 +/- 30 microM after 8 wk of training. The decrease in glutamine showed a strong positive correlation to the individual loss of CD4+ T cells (r = 0.67, P < 0.001). AET demonstrated a rise (P < 0.05) in GSH from 20.7 +/- 2.5 to 28.1 +/- 1.5 nmol/mg protein at terminal examination. In conclusion, our data indicate impairment of the number and activity of CD4+ T cells in response to 8 wk of ANT, which might be linked to metabolic factors such as glutamine.

scholarly journals Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders

2014 ◽  
Vol 211 (10) ◽  
pp. 2033-2045 ◽  
Author(s):  
Matthieu Perreau ◽  
Selena Vigano ◽  
Florence Bellanger ◽  
Céline Pellaton ◽  
Guillaume Buss ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Bacterial Translocation ◽  
Functional Impairment ◽  
Common Variable Immunodeficiency ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Ivig Treatment ◽  
Cell Functions ◽  
Common Variable

In the present study, we have investigated the functional profile of CD4 T cells from patients with common variable immunodeficiency (CVID), including production of cytokines and proliferation in response to bacteria and virus-derived antigens. We show that the functional impairment of CD4 T cells, including the reduced capacity to proliferate and to produce IFN-γ and IL-2, was restricted to bacteria-specific and not virus-specific CD4 T cells. High levels of endotoxins were found in the plasma of patients with CVID, suggesting that CD4 T cell dysfunction might be caused by bacterial translocation. Of note, endotoxemia was associated with significantly higher expression of programmed death 1 (PD-1) on CD4 T cells. The blockade of the PD-1–PD-L1/2 axis in vitro restored CD4 T cell proliferation capacity, thus indicating that PD-1 signaling negatively regulates CD4 T cell functions. Finally, we showed that intravenous immunoglobulin G (IVIG) treatment significantly reduced endotoxemia and the percentage of PD-1+ CD4 T cells, and restored bacteria-specific CD4 T cell cytokine production and proliferation. In conclusion, the present study demonstrates that the CD4 T cell exhaustion and functional impairment observed in CVID patients is associated with bacterial translocation and that IVIG treatment resolves bacterial translocation and restores CD4 T cell functions.

scholarly journals Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection

2015 ◽  
Vol 212 (9) ◽  
pp. 1449-1463 ◽  
Author(s):  
Egidio Torrado ◽  
Jeffrey J. Fountain ◽  
Mingfeng Liao ◽  
Michael Tighe ◽  
William W. Reiley ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Function ◽  
Killer Cell ◽  
Cell Number ◽  
Cd4 T Cell ◽  
Cell Phenotype ◽  
Mycobacterium Tuberculosis Infection

CD4+ T cells mediate protection against Mycobacterium tuberculosis (Mtb); however, the phenotype of protective T cells is undefined, thereby confounding vaccination efforts. IL-27 is highly expressed during human tuberculosis (TB), and absence of IL-27R (Il27ra) specifically on T cells results in increased protection. IL-27R deficiency during chronic Mtb infection does not impact antigen-specific CD4+ T cell number but maintains programmed death-1 (PD-1), CD69, and CD127 expression while reducing T-bet and killer cell lectin-like receptor G1 (KLRG1) expression. Furthermore, T-bet haploinsufficiency results in failure to generate KLRG1+, antigen-specific CD4+ T cells, and in improved protection. T cells in Il27ra−/− mice accumulate preferentially in the lung parenchyma within close proximity to Mtb, and antigen-specific CD4+ T cells lacking IL-27R are intrinsically more fit than intact T cells and maintain IL-2 production. Improved fitness of IL-27R–deficient T cells is not associated with increased proliferation but with decreased expression of cell death–associated markers. Therefore, during Mtb infection, IL-27R acts intrinsically on T cells to limit protection and reduce fitness, whereas the IL-27R–deficient environment alters the phenotype and location of T cells. The significant expression of IL-27 in TB and the negative influence of IL-27R on T cell function demonstrate the pathway by which this cytokine/receptor pair is detrimental in TB.

scholarly journals Distinctions Between CD8+ and CD4+ T-Cell Regenerative Pathways Result in Prolonged T-Cell Subset Imbalance After Intensive Chemotherapy

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3700-3707 ◽  
Author(s):  
Crystal L. Mackall ◽  
Thomas A. Fleisher ◽  
Margaret R. Brown ◽  
Mary P. Andrich ◽  
Clara C. Chen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Subset ◽  
Cd8 T Cell ◽  
Cell Number ◽  
Cd4 T Cell ◽  
Cell Regeneration ◽  
Intensive Chemotherapy ◽  
T Cell Subset

Abstract Rapid recovery of CD4+ T cells after intensive chemotherapy is limited by an age-dependent decline in thymopoiesis. Here we sought to determine whether similar limitations exist for CD8+ T-cell regeneration. After intensive chemotherapy, CD8+ T cells had a faster effective doubling time than CD4+ T cells (median, 12.6 v 28.2 days, P < .05). Accordingly, at 3 months posttherapy, mean CD8+ T-cell number had returned to baseline, whereas mean CD4+ T-cell number was only 35% of pretherapy values (P < .05). These differences were primarily due to very rapid expansion of CD8+CD57+ and CD8+CD28− subsets. At 3 months posttherapy, there was no relationship between age and CD8+ T-cell number (R = −.02), whereas CD4+ T-cell number was inversely related to age (R = −.66) and there were no discernible differences in CD8+ recovery among patients with or without thymic enlargement, whereas CD4+ recovery was enhanced in patients with thymic enlargement after chemotherapy (P < .01). Therefore thymic-independent pathways of T-cell regeneration appear to rapidly regenerate substantial numbers of CD8+, but not CD4+ T cells, resulting in prolonged T-cell subset imbalance after T-cell depletion. These inherent distinctions between CD4+v CD8+ T-cell regeneration may have significant implications for immunotherapeutic strategies undertaken to eradicate minimal residual neoplastic disease after cytoreductive chemotherapy.

scholarly journals Reduced immune-regulatory molecule expression on human colonic memory CD4 T cells in older adults

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Stephanie M. Dillon ◽  
Tezha A. Thompson ◽  
Allison J. Christians ◽  
Martin D. McCarter ◽  
Cara C. Wilson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Older Persons ◽  
Age Groups ◽  
T Cell Immunity ◽  
Cd4 T Cell ◽  
Cell Immunity ◽  
Memory Cd4 T Cells

Abstract Background The etiology of the low-level chronic inflammatory state associated with aging is likely multifactorial, but a number of animal and human studies have implicated a functional decline of the gastrointestinal immune system as a potential driver. Gut tissue-resident memory T cells play critical roles in mediating protective immunity and in maintaining gut homeostasis, yet few studies have investigated the effect of aging on human gut T cell immunity. To determine if aging impacted CD4 T cell immunity in the human large intestine, we utilized multi-color flow cytometry to measure colonic lamina propria (LP) CD4 T cell frequencies and immune-modulatory marker expression in younger (mean ± SEM: 38 ± 1.5 yrs) and older (77 ± 1.6 yrs) adults. To determine cellular specificity, we evaluated colon LP CD8 T cell frequency and phenotype in the same donors. To probe tissue specificity, we evaluated the same panel of markers in peripheral blood (PB) CD4 T cells in a separate cohort of similarly aged persons. Results Frequencies of colonic CD4 T cells as a fraction of total LP mononuclear cells were higher in older persons whereas absolute numbers of colonic LP CD4 T cells per gram of tissue were similar in both age groups. LP CD4 T cells from older versus younger persons exhibited reduced CTLA-4, PD-1 and Ki67 expression. Levels of Bcl-2, CD57, CD25 and percentages of activated CD38+HLA-DR+ CD4 T cells were similar in both age groups. In memory PB CD4 T cells, older age was only associated with increased CD57 expression. Significant age effects for LP CD8 T cells were only observed for CTLA-4 expression, with lower levels of expression observed on cells from older adults. Conclusions Greater age was associated with reduced expression of the co-inhibitory receptors CTLA-4 and PD-1 on LP CD4 T cells. Colonic LP CD8 T cells from older persons also displayed reduced CTLA-4 expression. These age-associated profiles were not observed in older PB memory CD4 T cells. The decline in co-inhibitory receptor expression on colonic LP T cells may contribute to local and systemic inflammation via a reduced ability to limit ongoing T cell responses to enteric microbial challenge.

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