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.

A mathematical model of HIV dynamics treated with a population of gene-edited haematopoietic progenitor cells exhibiting threshold phenomenon

2019 ◽  
Vol 37 (2) ◽  
pp. 212-242 ◽  
Author(s):  
Vardayani Ratti ◽  
Seema Nanda ◽  
Susan K Eszterhas ◽  
Alexandra L Howell ◽  
Dorothy I Wallace
Keyword(s):  
Mathematical Model ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Progenitor Cells ◽  
Cd4 T Cells ◽  
Gene Editing ◽  
Cd4 T Cell ◽  
Threshold Phenomenon ◽  
Cell Counts

Abstract The use of gene-editing technology has the potential to excise the CCR5 gene from haematopoietic progenitor cells, rendering their differentiated CD4-positive (CD4+) T cell descendants HIV resistant. In this manuscript, we describe the development of a mathematical model to mimic the therapeutic potential of gene editing of haematopoietic progenitor cells to produce a class of HIV-resistant CD4+ T cells. We define the requirements for the permanent suppression of viral infection using gene editing as a novel therapeutic approach. We develop non-linear ordinary differential equation models to replicate HIV production in an infected host, incorporating the most appropriate aspects found in the many existing clinical models of HIV infection, and extend this model to include compartments representing HIV-resistant immune cells. Through an analysis of model equilibria and stability and computation of $R_0$ for both treated and untreated infections, we show that the proposed therapy has the potential to suppress HIV infection indefinitely and return CD4+ T cell counts to normal levels. A computational study for this treatment shows the potential for a successful ‘functional cure’ of HIV. A sensitivity analysis illustrates the consistency of numerical results with theoretical results and highlights the parameters requiring better biological justification. Simulations of varying level production of HIV-resistant CD4+ T cells and varying immune enhancements as the result of these indicate a clear threshold response of the model and a range of treatment parameters resulting in a return to normal CD4+ T cell counts.

Relation of CD4+CD25+ Regulatory T Cells to Immune Status in Patients with HIV Infection.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3106-3106
Author(s):  
Sachi Tsunemi ◽  
Tsuyoshi Iwasaki ◽  
Takehito Imado ◽  
Satoshi Higasa ◽  
Eizo Kakishita ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Hiv Infection ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Healthy Controls ◽  
Cell Counts ◽  
Hiv 1

Abstract Human immunodeficiency virus (HIV) infection is characterized by marked defects in CD4+ helper T cell (Th) functions that commonly progress to a substantial decline in peripheral CD4+ T cell counts. However, the mechanisms responsible for the loss of Th functions in HIV-infected patients independent of CD4+ T cell counts remains unclear. CD4+CD25+ regulatory T cells (T Reg) are essential for down-regulation of both autoreactive and alloreactive T cells. Therefore, we decided to investigate the role of T Reg in immune status of HIV-infected patients. We examined the expression of cell surface CD25, cytoplasmic IL-4 and cytoplasmic IFN-gamma in peripheral blood CD4+ T cells from both healthy controls (n=9) and HIV-infected patients (n=43). We also compared T Reg functions between the 2 groups. CD4+CD25+ T Reg isolated from both HIV-infected patients and healthy controls strongly expressed CD45RO, HLA-DR, and FoxP3, and suppressed the proliferation of CD4+CD25− T cells, suggesting that CD4+CD25+ T cells from both healthy controls and HIV-infected patients possess phenotypic and functional characteristics of Treg. CD4+CD25high T cells are a subset of circulating CD4+CD25+ T cells in normal humans and exhibit strong in vitro regulatory functions similar to those reported for murine CD4+CD25+ T Reg. We measured the frequency of CD4+CD25high T Reg by analysis of surface CD25 on CD4+ T cells in peripheral blood samples. We also examined Th1 and Th2 frequencies by analysis of cytoplasmic IFN-gamma and IL-4 levels in CD4+ T cells. T Reg from HIV-infected patients with detectable plasma HIV-1 RNA showed a statistically significant increase in CD4+CD25high cell frequency (p<0.05) compared to healthy controls, with T Reg frequencies inversely proportional to CD4+ T cell numbers (p<0.01). However, in HIV-infected patients with undetectable plasma HIV-RNA, frequencies of CD4+CD25high T Reg were not increased and not related to CD4+ T cell numbers. In both HIV-infected patient groups, T Reg frequency was inversely related to Th1 frequency (detectable: p<0.05, undetectable: p<0.001), but positively related to Th2 frequency (detectable: p<0.01, undetectable: p<0.001). Our results indicate that increased frequencies of peripheral blood T Reg were related to disease progression as measured by detectable plasma HIV-1 RNA, decreased peripheral blood CD4+ T cell counts, and polarization toward Th2 immune responses in HIV-infected patients. HIV infection may lead to induction of T reg that inhibit antiviral immune responses, resulting in the progression of the disease. Manipulation of T Reg could help restore antiviral immune responses in HIV infection, and prevent the progression of HIV infection.

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 The effect of tuberculosis on immune reconstitution among HIV patients on highly active antiretroviral therapy in Adigrat general hospital, eastern Tigrai, Ethiopia; 2019: a retrospective follow up study

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Hadush Negash ◽  
Haftom Legese ◽  
Mebrahtu Tefera ◽  
Fitsum Mardu ◽  
Kebede Tesfay ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Immune Reconstitution ◽  
Cd4 T Cell ◽  
Highly Active ◽  
Cell Counts

Abstract Background Ethiopia initiated antiretroviral therapy early in 2005. Managing and detecting antiretroviral treatment response is important to monitor the effectiveness of medication and possible drug switching for low immune reconstitution. There is less recovery of CD4+ T cells among human immunodeficiency virus patients infected with tuberculosis. Hence, we aimed to assess the effect of tuberculosis and other determinant factors of immunological response among human immunodeficiency virus patients on highly active antiretroviral therapy. A retrospective follow up study was conducted from October to July 2019. A total of 393 participants were enrolled. An interviewer based questionnaire was used for data collection. Patient charts were used to extract clinical data and follow up results of the CD4+ T cell. Current CD4+ T cell counts of patients were performed. STATA 13 software was used to analyze the data. A p-value ≤0.05 was considered a statistically significant association. Results The mean age of study participants was 39.2 years (SD: + 12.2 years) with 8.32 mean years of follow up. The overall prevalence of immune reconstitution failure was 24.7% (97/393). Highest failure rate occurred within the first year of follow up time, 15.7 per 100 Person-year. Failure of CD4+ T cells reconstitution was higher among tuberculosis coinfected patients (48.8%) than mono-infected patients (13.7%). Living in an urban residence, baseline CD4+ T cell count ≤250 cells/mm3, poor treatment adherence and tuberculosis infection were significantly associated with the immunological failure. Conclusions There was a high rate of CD4+ T cells reconstitution failure among our study participants. Tuberculosis infection increased the rate of failure. Factors like low CD4+ T cell baseline count, poor adherence and urban residence were associated with the immunological failure. There should be strict monitoring of CD4+ T cell counts among individuals with tuberculosis coinfection.

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.

Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2912-2920 ◽  
Author(s):  
Marie-Lise Dion ◽  
Rebeka Bordi ◽  
Joumana Zeidan ◽  
Robert Asaad ◽  
Mohammed-Rachid Boulassel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Progression ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Cell Recovery ◽  
Cell Counts ◽  
Patients Experience

AbstractIn chronic HIV infection, most untreated patients lose naive CD4+ and CD8+ T cells, whereas a minority preserve them despite persistent high viremia. Although antiretroviral therapy (ART)–mediated viral suppression generally results in a rise of naive and total CD4+ T cells, certain patients experience very little or no T-cell reconstitution. High peripheral T-cell activation has been linked to poor clinical outcomes, interfering with previous evaluations of thymic function in disease progression and therapy-mediated T-cell recovery. To circumvent this, we used the sj/βTREC ratio, a robust index of thymopoiesis that is independent of peripheral T-cell proliferation, to evaluate the thymic contribution to the preservation and restoration of naive CD4+ T cells. We show that the loss of naive and total CD4+ T cells is the result of or is exacerbated by a sustained thymic defect, whereas efficient thymopoiesis supports naive and total CD4+ T-cell maintenance in slow progressor patients. In ART-treated patients, CD4+ T-cell recovery was associated with the normalization of thymopoiesis, whereas the thymic defect persisted in aviremic patients who failed to recover CD4+ T-cell counts. Overall, we demonstrate that efficient thymopoiesis is key in the natural maintenance and in therapy-mediated recovery of naive and total CD4+ T cells.

Increased levels of activated subsets of CD4 T cells add to the prognostic value of low CD4 T cell counts in a cohort of HIV-infected drug users

AIDS ◽  
2000 ◽  
Vol 14 (18) ◽  
pp. 2823-2829 ◽  
Author(s):  
Javier Carbone ◽  
Juana Gil ◽  
José M. Benito ◽  
Joaquín Navarro ◽  
Angeles Muñóz-Fernández ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Prognostic Value ◽  
Drug Users ◽  
Cd4 T Cell ◽  
Cell Counts

scholarly journals Longitudinal Analysis of Peripheral and Colonic CD161+ CD4+ T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1426
Author(s):  
Kerri Lal ◽  
Yuwadee Phuang-Ngern ◽  
Suchada Suhkumvittaya ◽  
Edwin Leeansyah ◽  
Aljawharah Alrubayyi ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
Cell Population ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Acute Hiv ◽  
Hiv 1

CD161 expression on CD4+ T cells is associated with a Th17 functional phenotype, as well as with an innate capacity to respond to interleukin (IL)-12 and IL-18 without T cell receptor (TCR) stimulation. Chronic HIV-1 infection is associated with loss of the CD161+ CD4 T cell population, and non-human primate studies suggest that their depletion is associated with disease progression. However, the dynamics of the CD161+ CD4+ T cell population during acute HIV-1 infection remains unknown. In this study, we characterize peripheral blood CD161+ CD4+ T cells in detail, and examine how they are affected during the earliest stages of HIV-1 infection. Unbiased surface proteome screening and principal component analysis indicated that CD161+ CD4+ T cells are relatively phenotypically homogeneous between donors, and are intermediates between conventional CD4 T cells and innate-like T cells. In acute untreated HIV-1 infection, the circulating CD161+ CD4+ T cell population decreased in frequency, as did absolute cell counts starting from peak viral load, with elevated levels of activation and exhaustion markers expressed throughout acute HIV-1 infection. The capacity of these cells to respond to stimulation with IL-12 and IL-18 was also reduced. Early initiation of anti-retroviral treatment (ART) during acute HIV-1 infection restored the functionality of peripheral blood CD161+ CD4+ T cells, but not their frequency. In contrast, early ART initiation prevented the decline of colonic CD161+ CD4+ T cells that otherwise started during acute infection. Furthermore, loss of peripheral and colonic CD161+ CD4+ T cells in untreated infection was associated with levels of viral load. These results suggest that acute HIV-1 infection has profound effects on the CD161+ CD4+ T cell population that could not be completely prevented by the initiation of ART.

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