scholarly journals 509. Comparision of CD4+ T Cells in Patients with Severe vs Critical COVID -19

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S320-S320
Author(s):  
Brenda Gomez-Gomez ◽  
Luis Espinosa-Aguilar ◽  
Javier Garcia-Guerrero ◽  
Irma Hoyo-Ulloa ◽  
Raquel Mendoza-Aguilar ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Invasive Mechanical Ventilation ◽  
Cd4 T Cell ◽  
The Mean ◽  
Critical Patients ◽  
Cd4 T Cell Count

Abstract Background Over the past few years, it has been shown that T cells play an essential role in antiviral immunity, in the course of the COVID-19 pandemic some studies reported an association between lymphocytopenia and exhaustion of the surviving remaining T cells which are apparently functional in patients with acute COVID-19, specially in those with severe forms of presentation. Some studies have reported an association where less than 800 CD4 + T cells are negatively related to the survival of seriously ill patients with COVID -19. Methods We included 19 patients admitted to our hospital (ABC Medical Center) from May 7 to 15, 2020 with a confirmed diagnosis of COVID-19 and were randomized into 2 groups according to the severity of the presentation (severe or critical) A determination of CD4 + T cells was made at admission, we also reported the need for invasive mechanical ventilation at some point of the hospitalization for each group, all patients were followed until their hospital discharge. One patient was excluded because he was still admitted at the time of the analysis. Results Of the 18 patients included, 9 (50%) fulfilled criteria of severe and 9 (50%) of critical. The mean of CD4 + T cell was 455 (256–697) for the severe and 285.44 (145–430) for the critical (CI 95% P 0.46), the determination of CD8+ T cell was 212 (88–392) for the severe and 201 (59–534) for the critical (CI 95% P 1.19), of the critical patients 8 (88.9%) required invasive mechanical ventilation and only one non-invasive mechanical ventilation, while the severe patients only required support with supplemental oxygen by nasal cannula (9 (100%)).The mean lenght of hospitalization was 12.73 days (3–34) and all the patients survived until they were discharged home. Conclusion As it has been reported in some studies, the pathogenesis of SARS-CoV-2 infection in humans is associated with a reduction and functional exhaustion of T cells in patients with COVID-19.In this study we presume that lower levels of CD4+T cells can be associated with critical forms of COVID 19 as the majority of critical patients in our report had < 300 CD4 +T cell count, while we need further studies with a greater number of patients and follow-up to establish reliable determinations, we propose than the levels of CD4+T cell count could be use as a good predictor of severity in COVID-19 Disclosures All Authors: No reported disclosures

scholarly journals Idiopathic CD4 T Cell Lymphocytopenia: A Case of Overexpression of PD-1/PDL-1 and CTLA-4

2021 ◽  
Vol 13 (1) ◽  
pp. 72-81
Author(s):  
Gaurav Kumar ◽  
Heidy Schmid-Antomarchi ◽  
Annie Schmid-Alliana ◽  
Michel Ticchioni ◽  
Pierre-Marie Roger
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Ex Vivo ◽  
Cd4 T Cell ◽  
Apoptotic Pathway ◽  
Cell Functions ◽  
Inhibitory Molecules ◽  
Cd4 T Cell Count ◽  
Costimulatory Pathway

Idiopathic CD4 T cell lymphocytopenia (ICL) is a rare entity characterized by CD4 T cell count of <300 cells/mm3 along with opportunistic infection for which T cell marker expression remains to be fully explored. We report an ICL case for which T lymphocyte phenotype and its costimulatory molecules expression was analyzed both ex vivo and after overnight stimulation through CD3/CD28. The ICL patient was compared to five healthy controls. We observed higher expression of inhibitory molecules PD-1/PDL-1 and CTLA-4 on CD4 T cells and increased regulatory T cells in ICL, along with high activation and low proliferation of CD4 T cells. The alteration in the expression of both the costimulatory pathway and the apoptotic pathway might participate to down-regulate both CD4 T cell functions and numbers observed in ICL.

Early Viral Load and CD4+T Cell Count, But Not Percentage of CCR5+or CXCR4+CD4+T Cells, Are Associated with R5-to-X4 HIV Type 1 Virus Evolution

2003 ◽  
Vol 19 (5) ◽  
pp. 389-398 ◽  
Author(s):  
Ronald P. van Rij ◽  
Mette D. Hazenberg ◽  
Birgit H.B. van Benthem ◽  
Sigrid A. Otto ◽  
Maria Prins ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
Cell Count ◽  
Cd4 T Cells ◽  
Virus Evolution ◽  
Cd4 T Cell ◽  
Hiv Type 1 ◽  
Cd4 T Cell Count

Nadir CD4+ T-cell count and numbers of CD28+ CD4+ T-cells predict functional responses to immunizations in chronic HIV-1 infection

AIDS ◽  
2003 ◽  
Vol 17 (14) ◽  
pp. 2015-2023 ◽  
Author(s):  
Christoph G Lange ◽  
Michael M Lederman ◽  
Kathy Medvik ◽  
Robert Asaad ◽  
Mary Wild ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Count ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Functional Responses ◽  
Hiv 1 ◽  
Cd4 T Cell Count

scholarly journals Validation of a Single-Platform, Volumetric, CD45-Assisted PanLeucogating Auto40 Flow Cytometer To Determine the Absolute Number and Percentages of CD4 T Cells in Resource-Constrained Settings Using Cameroonian Patients' Samples

2012 ◽  
Vol 19 (4) ◽  
pp. 609-615 ◽  
Author(s):  
François-Xavier Mbopi-Kéou ◽  
Stefano Mion ◽  
Bertrand Sagnia ◽  
Laurent Bélec
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Flow Cytometer ◽  
Cd4 T Cell ◽  
Resource Constrained ◽  
Limits Of Agreement ◽  
Cell Counts ◽  
Absolute Bias ◽  
The Mean

ABSTRACTThe study evaluated the single-platform, volumetric, CD45-assisted PanLeucogating Auto40 flow cytometer (Apogee Flow Systems Ltd., Hemel Hempstead, United Kingdom) for CD4 T cell numeration, compared to the reference FACSCalibur flow cytometer. Results of absolute counts and percentages of CD4 T cells by Auto40 and FACSCalibur of 234 tripotassium EDTA (K3-EDTA)-blood samples from 146 adults and 88 children (aged from 18 months to 5 years), living in Yaoundé, Cameroon, were highly correlated (r2= 0.97 andr2= 0.98, respectively). The mean absolute bias and relative bias between Apogee Auto40 and FACSCalibur absolute CD4 T cell counts were +9.6 cells/μl, with limits of agreement from −251 to 270 cells/μl, and +4.1%, with limits of agreement from −16.1 to 24.4%, respectively. The mean absolute bias and relative bias between Apogee Auto40 and FACSCalibur CD4 T cell results expressed as percentages were +0.05% CD4 (95% confidence interval [CI], −0.03 to 0.41), with limits of agreement from −6.0 to 5.9% CD4, and +1.0%, with limits of agreement from −32.3 to 34.4%, respectively. The Auto40 counting allowed identification of the majority of adults with CD4 T cell counts below 200 cells/μl (sensitivity, 87%; specificity, 98%) or below 350 cells/μl (sensitivity, 92%; specificity, 98%) and of children with CD4 T cell counts below 750 cells/μl (sensitivity, 82%; specificity, 98%) or below 25% CD4+(sensitivity, 96%; specificity, 99%). The Auto40 analyzer is a reliable alternative flow cytometer for CD4 T lymphocyte enumeration to be used in routine immunological monitoring according to the WHO recommendations for HIV-infected adults as well as children living in resource-constrained settings.

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.

scholarly journals The Impact of Exercise Serum on Selected Parameters of CD4+ T Cell Metabolism

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 119-131
Author(s):  
Jana Palmowski ◽  
Kristina Gebhardt ◽  
Thomas Reichel ◽  
Torsten Frech ◽  
Robert Ringseis ◽  
...  
Keyword(s):  
T Cells ◽  
Oxygen Consumption ◽  
T Cell ◽  
Real Time ◽  
Cd4 T Cells ◽  
Cell Metabolism ◽  
Cd4 T Cell ◽  
Autologous Serum ◽  
Cell Phenotype ◽  
The Impact

CD4+ T cells are sensitive to peripheral changes of cytokine levels and metabolic substrates such as glucose and lactate. This study aimed to analyze whether factors released after exercise alter parameters of human T cell metabolism, specifically glycolysis and oxidative phosphorylation. We used primary human CD4+ T cells activated in the presence of autologous serum, which was collected before (CO) and after a 30-min exercise intervention (EX). In the course of activation, cells and supernatants were analyzed for cell viability and diameter, real-time oxygen consumption by using PreSens Technology, mRNA expression of glycolytic enzymes and complexes of the electron transport chain by real-time PCR, glucose, and lactate levels in supernatants, and in vitro differentiation by flow cytometry. EX did not alter T cell phenotype, viability, or on-blast formation. Similarly, no difference between CO and EX were found for CD4+ T cell activation and cellular oxygen consumption. In contrast, higher levels of glucose were found after 48 h activation in EX conditions. T cells activated in autologous exercise serum expressed lower HK1 mRNA and higher IFN-γ receptor 1. We suggest that the exercise protocol used was not sufficient to destabilize the immune metabolism of T cells. Therefore, more intense and prolonged exercise should be used in future studies.

scholarly journals HIV-Related Arterial Stiffness in Malawian Adults Is Associated With the Proportion of PD-1–Expressing CD8+ T Cells and Reverses With Antiretroviral Therapy

2019 ◽  
Vol 219 (12) ◽  
pp. 1948-1958 ◽  
Author(s):  
Christine Kelly ◽  
Henry C Mwandumba ◽  
Robert S Heyderman ◽  
Kondwani Jambo ◽  
Raphael Kamng’ona ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Arterial Stiffness ◽  
Cell Count ◽  
Cd8 T Cells ◽  
Sub Saharan Africa ◽  
Cd4 T Cell ◽  
Sub Saharan ◽  
Cd4 T Cell Count

Abstract Background The contribution of immune activation to arterial stiffness and its reversibility in human immunodeficiency virus (HIV)–infected adults in sub-Saharan Africa is unknown. Methods HIV-uninfected and HIV-infected Malawian adults initiating antiretroviral therapy (ART) with a CD4+ T-cell count of &lt;100 cells/μL were enrolled and followed for 44 weeks; enrollment of infected adults occurred 2 weeks after ART initiation. We evaluated the relationship between carotid femoral pulse wave velocity (cfPWV) and T-cell activation (defined as HLA-DR+CD38+ T cells), exhaustion (define as PD-1+ T cells), and senescence (defined as CD57+ T cells) and monocyte subsets, using normal regression. Results In 279 HIV-infected and 110 HIV-uninfected adults, 142 (37%) had hypertension. HIV was independently associated with a 12% higher cfPWV (P = .02) at baseline and a 14% higher cfPWV at week 10 (P = .02), but the increases resolved by week 22. CD4+ and CD8+ T-cell exhaustion were independently associated with a higher cfPWV at baseline (P = .02). At 44 weeks, arterial stiffness improved more in those with greater decreases in the percentage of CD8+ T cells and the percentage of PD-1+CD8+ T cells (P = .01 and P = .03, respectively). When considering HIV-infected participants alone, the adjusted arterial stiffness at week 44 tended to be lower in those with higher baseline percentage of PD-1+CD8+ T cells (P = .054). Conclusions PD-1+CD8+ T-cells are associated with HIV-related arterial stiffness, which remains elevated during the first 3 months of ART. Resources to prevent cardiovascular disease in sub-Saharan Africa should focus on blood pressure reduction and individuals with a low CD4+ T-cell count during early ART.

scholarly journals Infection of HLA-DR1 Transgenic Mice with a Human Isolate of Influenza A Virus (H1N1) Primes a Diverse CD4 T-Cell Repertoire That Includes CD4 T Cells with Heterosubtypic Cross-Reactivity to Avian (H5N1) Influenza Virus

2009 ◽  
Vol 83 (13) ◽  
pp. 6566-6577 ◽  
Author(s):  
Katherine A. Richards ◽  
Francisco A. Chaves ◽  
Andrea J. Sant
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Cd4 T Cells ◽  
Cross Reactivity ◽  
Cd4 T Cell ◽  
Ns1 Protein ◽  
Infected Cells

ABSTRACT The specificity of the CD4 T-cell immune response to influenza virus is influenced by the genetic complexity of the virus and periodic encounters with variant subtypes and strains. In order to understand what controls CD4 T-cell reactivity to influenza virus proteins and how the influenza virus-specific memory compartment is shaped over time, it is first necessary to understand the diversity of the primary CD4 T-cell response. In the study reported here, we have used an unbiased approach to evaluate the peptide specificity of CD4 T cells elicited after live influenza virus infection. We have focused on four viral proteins that have distinct intracellular distributions in infected cells, hemagglutinin (HA), neuraminidase (NA), nucleoprotein, and the NS1 protein, which is expressed in infected cells but excluded from virion particles. Our studies revealed an extensive diversity of influenza virus-specific CD4 T cells that includes T cells for each viral protein and for the unexpected immunogenicity of the NS1 protein. Due to the recent concern about pandemic avian influenza virus and because CD4 T cells specific for HA and NA may be particularly useful for promoting the production of neutralizing antibody to influenza virus, we have also evaluated the ability of HA- and NA-specific CD4 T cells elicited by a circulating H1N1 strain to cross-react with related sequences found in an avian H5N1 virus and find substantial cross-reactivity, suggesting that seasonal vaccines may help promote protection against avian influenza virus.

scholarly journals Isolevuglandin-Modified Cardiac Proteins Drive CD4+ T Cell Activation in the Heart and Promote Cardiac Dysfunction

Circulation ◽  
2021 ◽  
Author(s):  
Njabulo Ngwenyama ◽  
Annet Kirabo ◽  
Mark Aronovitz ◽  
Francisco Velázquez ◽  
Francisco Carrillo-Salinas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cardiac Dysfunction ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Myocardial Oxidative Stress

Background: Despite the well-established association between T cell-mediated inflammation and non-ischemic heart failure (HF), the specific mechanisms triggering T cell activation during the progression of HF and the antigens involved are poorly understood. We hypothesized that myocardial oxidative stress induces the formation of isolevuglandin (IsoLG)-modified proteins that function as cardiac neoantigens to elicit CD4+ T cell receptor (TCR) activation and promote HF. Methods: We used transverse aortic constriction (TAC) in mice to trigger myocardial oxidative stress and T cell infiltration. We profiled the TCR repertoire by mRNA sequencing of intramyocardial activated CD4+ T cells in Nur77 GFP reporter mice, which transiently express GFP upon TCR engagement. We assessed the role of antigen presentation and TCR specificity in the development of cardiac dysfunction using antigen presentation-deficient MhcII -/- mice, and TCR transgenic OTII mice that lack specificity for endogenous antigens. We detected IsoLG-protein adducts in failing human hearts. We also evaluated the role of reactive oxygen species (ROS) and IsoLGs in eliciting T cell immune responses in vivo by treating mice with the antioxidant TEMPOL, and the IsoLG scavenger 2-hydroxybenzylamine (2-HOBA) during TAC, and ex-vivo in mechanistic studies of CD4+ T cell proliferation in response to IsoLG-modified cardiac proteins. Results: We discovered that TCR antigen recognition increases in the left ventricle (LV) as cardiac dysfunction progresses, and identified a limited repertoire of activated CD4+ T cell clonotypes in the LV. Antigen presentation of endogenous antigens was required to develop cardiac dysfunction since MhcII -/- mice reconstituted with CD4+ T cells, and OTII mice immunized with their cognate antigen were protected from TAC-induced cardiac dysfunction despite the presence of LV-infiltrated CD4+ T cells. Scavenging IsoLGs with 2-HOBA reduced TCR activation and prevented cardiac dysfunction. Mechanistically, cardiac pressure overload resulted in ROS dependent dendritic cell accumulation of IsoLG-protein adducts which induced robust CD4+ T cell proliferation. Conclusions: Collectively, our study demonstrates an important role of ROS-induced formation of IsoLG-modified cardiac neoantigens that lead to TCR-dependent CD4+ T cell activation within the heart.

scholarly journals PIMATM point-of-care testing for CD4 counts in predicting antiretroviral initiation in HIV-infected individuals in KwaZulu-Natal, Durban, South Africa

2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Mandisa Skhosana ◽  
Shabashini Reddy ◽  
Tarylee Reddy ◽  
Siphelele Ntoyanto ◽  
Elizabeth Spooner ◽  
...  
Keyword(s):  
South Africa ◽  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Point Of Care ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Kwazulu Natal ◽  
Cd4 T Cell Count

Introduction: Limited information is available on the usefulness of the PIMATM analyser in predicting antiretroviral treatment eligibility and outcome in a primary healthcare clinic setting in disadvantaged communities in KwaZulu-Natal, South Africa.Materials and methods: The study was conducted under the eThekwini Health Unit, Durban, KwaZulu-Natal. Comparison of the enumeration of CD4+ T-cells in 268 patients using the PIMATM analyser and the predicate National Health Laboratory Services (NHLS) was undertaken during January to July 2013. Bland-Altman analysis to calculate bias and limits of agreement, precision and levels of clinical misclassification at various CD4+ T-cell count thresholds was performed.Results: There was high precision of the PIMATM control bead cartridges with low and normal CD4+ T-cell counts using three different PIMATM analysers (%CV < 5). Under World Health Organization (WHO) guidelines (≤ 500 cells/mm3), the sensitivity of the PIMATM analyser was 94%, specificity 78% and positive predictive value (PPV) 95%. There were 24 (9%) misclassifications, of which 13 were false-negative in whom the mean bias was 149 CD4+ T-cells/mm3. Most (87%) patients returned for their CD4 test result but only 67% (110/164) of those eligible (≤ 350 cells/mm3) were initiated on antiretroviral therapy (ART) with a time to treatment of 49 days (interquartile range [IQR], 42–64 days).Conclusion: There was adequate agreement between PIMATM analyser and predicate NHLS CD4+ T-cell count enumeration (≤ 500 cells/mm3) in adult HIV-positive individuals. The high PPV, sensitivity and acceptable specificity of the PIMATM analyser technology lend it as a reliable tool in predicting eligibility and rapid linkage to care in ART programmes.Keywords: HIV; Point of Care; PIMATM CD4+ T cell counts; antiretroviral therapy; prediction/eligibility; South Africa

Sign in / Sign up

Export Citation Format

Share Document