scholarly journals Age-dependent normalisation functions for T-lymphocytes in healthy individuals

2021 ◽  
Author(s):  
Juliane Schröter ◽  
José A. M. Borghans ◽  
W. Marieke Bitter ◽  
Jacques J. M. van Dongen ◽  
Rob J. de Boer
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Cell Subset ◽  
Initial Time ◽  
Parameter Estimates ◽  
Cell Recovery ◽  
T Lymphocyte Subsets ◽  
Cell Counts ◽  
Total Lymphocyte

AbstractLymphocyte numbers naturally change through age. Normalisation functions to account for this are sparse, and mostly disregard measurements from children in which these changes are most prominent. In this study, we analyse cross-sectional numbers of mainly T-lymphocytes (CD3+, CD3+CD4+ and CD3+CD8+) and their subpopulations (naive and memory) from 673 healthy Dutch individuals ranging from infancy to adulthood (0-62 years). We fitted the data by a delayed exponential function and received parameter estimates for each lymphocyte subset. Our modelling approach follows general laboratory measurement procedures in which absolute cell counts of T-lymphocyte subsets are calculated from observed percentages within a reference population that is truly counted (typically the total lymphocyte count). Consequently, we receive one set of parameter estimates per T-cell subset representing both the trajectories of their counts and percentages. We allow for an initial time delay of half a year before the total lymphocyte counts per µl of blood start to change exponentially, and we find that T-lymphocyte trajectories tend to increase during the first half a year of life. Thus, our study provides functions describing the general trajectories of T-lymphocyte counts and percentages of the Dutch population. These functions provide important references to study T-lymphocyte dynamics in disease, and allow one to quantify losses and gains in longitudinal data, such as the CD4+ T-cell decline in HIV-infected children, and/or the rate of T-cell recovery after the onset of treatment.

scholarly journals ROLE OF DISTINCT CD4+ T-CELL SUBSETS IN HIV-INFECTION PATHOGENESIS

2020 ◽  
pp. 236-246
Author(s):  
E. V. Saidakova ◽  
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Lymphocytes ◽  
Hiv Infection ◽  
T Lymphocyte ◽  
Highly Active Antiretroviral Therapy ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
T Lymphocyte Subsets

CD4+ T-cell pool is composed of cells residing in different maturation stages. Naive CD4+ T-lymphocytes, CD4+ stem memory T-cells, CD4+ central and effector memory T-lymphocytes perform var-ious functions in maintaining the immune system homeostasis. Despite phenotypic differences, each of those cells can be infected with HIV. Specific features of distinct CD4+ T-lymphocyte subsets determine their role in HIV-infection pathogenesis. By analyzing changes of CD4+ T-lymphocyte subset composi-tion, one can estimate the degree of the immune system damage and make predictions of immune recov-ery under highly active antiretroviral therapy. The article summarizes the main events occurring with CD4+ T-cell subsets during HIV-infection.

Changes in L-Selectin Expression by T Lymphocytes after Extracorporeal Photochemotherapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1961-1961
Author(s):  
Manuel Ramirez ◽  
Marta Gonzalez-Vicent ◽  
Antonio Perez-Martinez ◽  
Julian Sevilla ◽  
Luis Madero ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Receptor Activation ◽  
P Value ◽  
T Lymphocyte Subsets ◽  
Extracorporeal Photochemotherapy ◽  
Steroid Refractory

Abstract Extracorporeal photochemotherapy (ECP) is an emerging treatment modality for steroid-refractory acute and chronic graft versus host disease (GVHD). The mechanisms by which ECP works are still not fully understood, and modulation of dendritic cell subpopulations, a shift of cytokine profile from Th1 to Th2 and an increase of T-cell regulatory (Treg) cells have been related to the ECP beneficial effect. Changes on T-lymphocyte subsets other than Treg have been reported after ECP (Biol Blood Marrow Transplant2006; 12(1 Suppl 2):22–30.). We analyzed the effect of ECP on the T lymphocyte subsets of sixteen children receiving this form of therapy. Steroid refractory GVHD was defined as failure to respond to 2 mg/Kg/day of methylprednisolone after 5 days (acute GVHD) or failure to respond to steroids or flare of disease activity upon tapering (chronic GVHD). ECP was performed by an alternative approach to that of the classical UVAR XTS system. This alternative method is based on a continuous-flow cell separator (COBE Spectra) that allow to process more mononuclear cells in a smaller volume and it is less time-consuming, both important advantages for pediatric patients. We studied the L-selectin (CD62L) and the CD45RA expression on CD4 and CD8 lymphocytes by flow cytometry. This combination allowed us to distinguish naive (TN, CD62L+CD45RA+), central memory (TCM, CD62L+CD45RA+), effector memory (TEM, CD62L+CD45RA+), and terminal differentiated T cells (TT, CD62L+CD45RA+), as described in Science2000;290:92–97. We compared the proportion of each of these four subpopulations, as well as the L-selectin positive and L-selectin negative ones, in samples collected from peripheral blood before the first (PRE) and after the last (POST) ECP procedures. Statistical analyses were done by the Wilcoxon signed-rank test. Results are shown in the following tables: CD4 SUBSETS & ECP PRE POST p value TN 6.58 ± 2.39 6.18 ± 2.96 0.2003 TCM 58.17 ± 4.49 43.85 ± 4.78 0.0268 TEM 34.64 ± 4.51 46.86 ± 4.89 0.0356 TT 0.6 ± 0.18 3.11 ± 1.46 0.1704 CD62Lpos 64.76 ± 4.4 50.03 ± 5.45 0.0268 CD62Lneg 35.23 ± 4.4 49.97 ± 5.45 0.0268 CD8 SUBSETS & ECP PRE POST p value TN 16.95 ± 3.94 12.53 ± 4.05 0.2343 TCM 28.8 ± 4.95 12.27 ± 2.86 0.0013 TEM 46.62 ± 5.79 51.4 ± 4.22 0.1477 TT 11.17 ± 3.34 23.52 ± 4.79 0.0105 CD62Lpos 45.75 ± 6.1 24.8 ± 5.34 0.0174 CD62Lneg 53.8 ± 6.07 74.92 ± 5.31 0.0174 The clinical outcome of the patients was always positive, with more than 50% achieving complete remission. The proportion of L-selectin expressing T lymphocytes significantly diminished after ECP, both in CD4 and in CD8 cells. The reason for these changes are currently unknown. L-selectin is an important T-cell homing receptor for T-cell entry into lymph nodes via high endothelial venules. Expression of CD62L is rapidly lost following T-cell receptor activation, leading to exit from the lymph node into the periphery and sites of inflammation. CD62Lneg and CD62Lpos also differ in their functional abilities, such as cytokine secretion and cytolytic potential. Our results suggest that ECP may have an impact in the trafficking patterns of T lymphocytes, redirectioning T cells from lymphoid to extralymphoid organs. In addition, ECP was associated to a redistribution of the pool of non-naive T lymphocytes.

scholarly journals Flow cytometric analysis of T lymphocytes and cytokines in aqueous humor of patients with varicella zoster virus-mediated acute retinal necrosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hao Kang ◽  
Yunbo Wei ◽  
Ming Liu ◽  
Di Yu ◽  
Yong Tao
Keyword(s):  
T Lymphocytes ◽  
Varicella Zoster Virus ◽  
Aqueous Humor ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Flow Cytometric Analysis ◽  
T Lymphocyte Subsets ◽  
Varicella Zoster ◽  
Flow Cytometric ◽  
Cd8 T Lymphocytes

Abstract Background The purpose of this study is to investigate the aqueous humor (AH) T lymphocyte subsets and cytokines of acute retinal necrosis (ARN) to elucidate the immunologic inflammatory features of this disorder. Methods Three patients with ARN infected with varicella zoster virus (VZV) who underwent multiple intravitreal injections of ganciclovir were enrolled in this study. The control group consisted of four non-infectious patients with acute anterior uveitis (AAU). Flow cytometric analysis was performed on the lymphocyte subsets from the AH and peripheral blood (PB) samples during the active phase of intraocular inflammation. Five inflammatory cytokines were measured in each AH sample and various clinical characteristics were also assessed. Results VZV deoxyribonucleic acid (DNA) was detected by real-time polymerase chain reaction (PCR) in AH from all the ARN patients, who showed higher CD8+ T lymphocytes population in AH than the AAU patients (p = 0.006). CD4/CD8 ratios of T lymphocytes and the percentage of CD8 + CD25+ T lymphocytes in AH were significantly lower in ARN than in AAU (p = 0.006; p = 0.012). In the ARN patients, the percentages of CD4+ and CD8+ T lymphocytes in AH were higher than those found in PB. The percentage of CD4 + CD25+ T lymphocytes in AH was significantly higher than the proportion in PB in the AAU patients (p = 0.001). Immunoregulatory cytokine Interleukin-10 in AH was significantly elevated in the ARN patients in comparison with the case of the AAU patients (p = 0.036). In ARN, the copy number of VZV DNA in AH positively correlated with the percentage of CD8+ T lymphocytes in AH and negatively correlated with the CD4/CD8 ratio in AH during the course of disease treatment (p = 0.009, r = 0.92; p = 0.039, r = − 0.834). Conclusion The ARN patients caused by VZV had different intraocular T lymphocyte subsets and cytokines profile than those of the non-infectious patients. High percentages of CD8+ T lymphocytes and low CD4/CD8 T cell ratios may be a potential biomarker for diagnosis of viral-infectious uveitis. T lymphocytes examination at the inflammatory sites has the potential to become a useful research tool for differentiating viral and non-viral uveitis.

scholarly journals Long-Term Depletion of Naive T Cells in Patients Treated for Hodgkin's Disease

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3662-3672 ◽  
Author(s):  
Nobukazu Watanabe ◽  
Stephen C. De Rosa ◽  
Anthony Cmelak ◽  
Richard Hoppe ◽  
Leonore A. Herzenberg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Cell Counts

Abstract We investigated the representation of T cells in patients who had been treated for Hodgkin's disease (HD). We found a marked depletion in both CD4 and CD8 naive T-cell counts that persists up to 30 years after completion of treatment. In contrast, CD4 and CD8 memory T-cell subsets recovered to normal or above normal levels by 5 years posttreatment. Thus, the previously-reported long-term deficit in total CD4 T-cell counts after treatment for HD is due to specific depletion of naive T cells. Similarly, total CD8 T-cell counts return to normal by 5 years only because CD8 memory T cells expand to higher than normal levels. These findings suggest that the treatment (mediastinal irradiation) results in a longterm dysregulation of T-cell subset homeostasis. The profound depletion of naive T cells may explain the altered T-cell function in treated patients, including the poor response to immunization after treatment for HD. Further, in some individuals, we identified expansions of unusual subsets expressing low levels of CD8. Eight-color fluorescence-activated cell sorting analyses showed that these cells largely express CD8αα homodimers and CD57, consistent with the phenotype of potentially extrathymically derived T cells. In addition, these cells, both CD4+ and CD4−, are probably cytotoxic lymphocytes, as they express high levels of intracellular perforin. In adults treated for HD, an increased activity of extrathymic T-cell differentiation may partially compensate for the loss of thymic-derived T cells.

Correlation between total and CD4 lymphocyte counts in HIV infection: not making the good an enemy of the not so perfect

1996 ◽  
Vol 7 (6) ◽  
pp. 422-428 ◽  
Author(s):  
E J Beck ◽  
E J Kupek ◽  
M M Gompels ◽  
A J Pinching
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Lymphocyte Count ◽  
Cell Subset ◽  
Total Lymphocyte Count ◽  
Aids Patients ◽  
T Cell Subset ◽  
Total Lymphocyte ◽  
Asymptomatic Patients ◽  
Cd4 Lymphocyte

The aim of this study was to assess the correlation and average cost of total lymphocyte count compared with CD4 count as a broad estimate of immunosuppression in HIV-1 infected individuals. Spearman's partial rank correlation were calculated between total lymphocyte count, absolute CD4 count and CD4 per cent stratified by stage of HIV-1 infection for routinely collected samples. Data were collected prospectively from a T cell-subset register combined with clinical data obtained retrospectively from case notes of HIV-infected patients managed at St Mary's Hospital, London 1982-1991. Costing data were obtained through a survey of the departments of haematology and immunology 1989 90 prices . The correlation between 1534 paired absolute lymphocyte count and CD4 lymphocyte count was found to be high R 0.76 . When analysed by stage of HIV infection, the correlation increased from R 0.64 for asymptomatic patients, to R 0.72 for patients with symptomatic non-AIDS HIV infection and R 0.73 for AIDS patients. Correlations between absolute lymphocyte count and CD4 per cent were considerably weaker: R 0.41 all paired counts; R 0.32 for asymptomatic patients; R 0.25 for symptomatic non-AIDS patients; R 0.32 for AIDS patients. Average cost was 8 per full blood count compared with 38 per T-cell subset analysis. The high correlation between total and CD4 lymphocyte counts, especially for patients with symptomatic HIV disease, demonstrates the suitability of the use of total lymphocyte count in the absence of CD4 counts. Given the considerably lower prices of total lymphocyte counts compared with T-cell subset analysis, this is particularly relevant for developing countries.

scholarly journals Assessment of the Percentages of T-lymphocyte Subsets in the Peripheral Blood of Mediterranean Spotted Fever Patients

2020 ◽  
Vol 18 (2) ◽  
pp. 111-119
Author(s):  
Iv. Baltadzhiev ◽  
P. Pavlov
Keyword(s):  
T Cells ◽  
Disease Severity ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Spotted Fever ◽  
Healing Process ◽  
Cell Subset ◽  
Rickettsia Conorii ◽  
Mediterranean Spotted Fever ◽  
T Lymphocyte Subsets

Purpose: Mediterranean spotted fever (MSF) is a rickettsial disease. The aim was to evaluate the host immunе response to Rickettsia conorii. Material and methods: 62 patients were assigned into three groups: with mild, moderate or severe clinical forms of MSF. Controls were 32 healthy individuals. The diagnosis of MSF was confirmed by the indirect immunofluorescence assay. Immunophenotyping was performed using Epics XL-MCL Coulter. Results: The percentage of immune competent (CD3+) cells decreased, whereas that of helper/inducer (CD3+CD4+) and suppressor/cytotoxic (CD3+CD8+) did not change compared to controls. All three T-cell subset percentages did not parallel the disease severity. Naïve T-cells (CD4+CD45RA+) showed reduced levels, whereas activated memory (CD4+CD45RO+) T-cells did not change significantly. The percentage of activated (CD3+HLA-DR+) T-cells increased regardless of the disease severity, till the rise of stimulatory molecules (CD38+total) matched the disease severity forms. The percentage of costimulatory CD28-molecules corresponded to the disease severity as their levels increased significantly in mild forms and showed an evident downward trend towards the severe ones. Conclusion: Reduced T-lymphocyte subsets are likely related to trans-migration into perivascular inflammatory foci. The increased percentage of T-lymphocytes armed with stimulatory molecules probably reflects the mobilization of cell-mediated immune response in the healing process.

Flow Cytometric Analysis of T Lymphocytes and Cytokines in Aqueous Humor of Patients with Varicella Zoster Virus-mediated Acute Retinal Necrosis

2020 ◽  
Author(s):  
Hao Kang ◽  
Yunbo Wei ◽  
Ming Liu ◽  
Di Yu ◽  
Yong Tao
Keyword(s):  
T Lymphocytes ◽  
Varicella Zoster Virus ◽  
Aqueous Humor ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Flow Cytometric Analysis ◽  
T Lymphocyte Subsets ◽  
Varicella Zoster ◽  
Flow Cytometric ◽  
Cd8 T Lymphocytes

Abstract Background: The purpose of this study is to investigate the aqueous humor (AH) T lymphocyte subsets and cytokines of acute retinal necrosis (ARN) to elucidate the immunologic inflammatory features of this disorder.Methods: Three patients with ARN infected with varicella zoster virus (VZV) who underwent multiple intravitreal injections of ganciclovir were enrolled in this study. The control group consisted of four non-viral infectious patients with acute anterior uveitis (AAU). Flow cytometric analysis was performed on the lymphocyte subsets from the AH and peripheral blood (PB) samples during the active phase of intraocular inflammation. Five inflammatory cytokines were measured in each AH sample and various clinical characteristics were also assessed.Results: VZV DNA was detected by real-time polymerase chain reaction (PCR) in AH from all the ARN patients, who showed higher CD8+ T lymphocytes population in AH than the AAU patients (p=0.006). CD4/CD8 ratios of T lymphocytes and the percentage of CD8+CD25+ T lymphocytes in AH were significantly lower in ARN than in AAU (p=0.006; p=0.012). In the ARN patients, the percentages of CD4+ and CD8+ T lymphocytes in AH were higher than those found in PB. The percentage of CD4+CD25+ T lymphocytes in AH was significantly higher than the proportion in PB in the AAU patients (p=0.001). Immunoregulatory cytokine Interleukin-10 in AH was significantly elevated in the ARN patients in comparison with the case of the AAU patients (p=0.036). In ARN, the copy number of VZV DNA in AH positively correlated with the percentage of CD8+ T lymphocytes in AH and negatively correlated with the CD4/CD8 ratio in AH during the course of disease treatment (p=0.009, r=0.92; p=0.039, r=-0.834).Conclusion: The ARN patients caused by VZV had different intraocular T lymphocyte subsets and cytokines profile than those of the non-viral infectious patients. High percentages of CD8+ T lymphocytes and low CD4/CD8 T cell ratios may be a potential biomarker for diagnosis of viral-infectious uveitis. T lymphocytes examination at the inflammatory sites has the potential to become a useful research tool for differentiating viral and non-viral uveitis.

scholarly journals Prediction of CD4 T-Lymphocyte Count Using WHO Clinical Staging among ART-Naïve HIV-Infected Adolescents and Adults in Northern Ethiopia: A Retrospective Study

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Abraham Desta Aregay ◽  
Kibriti Mehari Kidane ◽  
Asfawosen Berhe Aregay ◽  
Kiros Ajemu Fenta ◽  
Ataklti Gebretsadik Woldegebriel ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Lymphocyte Count ◽  
Cd4 Count ◽  
Cd4 T Cell ◽  
Clinical Staging ◽  
Northern Ethiopia ◽  
Immunological Status ◽  
Cell Counts ◽  
Adolescents And Adults

Background. WHO clinical staging has long been used to assess the immunological status of HIV-infected patients at initiation of antiretroviral therapy and during treatment follow-up. In setups where CD4 count determination is not readily available, WHO clinical staging is a viable option. However, correlation between CD4 count and WHO clinical staging is not known in an Ethiopian setting, and hence, the main aim of this study was to assess predictability of CD4 T-lymphocyte count using WHO clinical staging among ART-naïve HIV-infected adolescents and adults in northern Ethiopia. Methods. A retrospective cross-sectional study was done in the Tigray Region, Ethiopia, from April 2015 to January 2019 from a secondary database of 19525 HIV-infected patients on antiretroviral treatment. Analysis was done using STATA-14.0 to estimate the frequencies, mean, and median of CD4 T-cell count in each WHO stages. Sensitivity, specificity, positive predictive value, negative predictive value, kappa test, and correlations were calculated to show the relationships between WHO stages and CD T-cell count. Results. The sensitivity of WHO clinical staging to predict CD4 T-cell counts of <200 cells/μl was 94.17% with a specificity of 3.62%. The PPV was 49.03%, and the NPV was 3.62%. The sensitivity of WHO clinical staging to predict CD4 T-cell counts of <350 cells/μl was 94.75% with a specificity of 3.00%. The PPV was 75.81%, and the NPV was 15.09%. Similarly, the sensitivity of WHO clinical staging to predict CD4 T-cell counts of <500 cells/μl was 95.03% with a specificity of 2.73% and the PPV and NPV were 88.32% and 6.62%, respectively. The kappa agreement of WHO clinical stages was also insignificant when compared with the disaggregated CD4 counts in different categories. The correlation of WHO clinical staging was inversely associated with the CD4 count, and the magnitude of the correlation was 5.22%. Conclusions. The WHO clinical staging had high sensitivity but low specificity in predicting patients with CD4 count <200 cells/μl, <350 cells/μl, and <500 cells/μl. There was poor correlation and agreement between CD4 T-lymphocyte count and WHO clinical staging. Therefore, WHO clinical staging alone may not provide accurate information on the immunological status of patients, and hence, it is better to use the CDC definition rather than the WHO clinical definition.

scholarly journals X4-Tropic Latent HIV-1 Is Enriched in Peripheral Follicular Helper T Cells and Is Correlated with Disease Progression

2019 ◽  
Vol 94 (2) ◽  
Author(s):  
Fei Yu ◽  
Qijuan Li ◽  
Xi Chen ◽  
Jun Liu ◽  
Linghua Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Disease Progression ◽  
Clinical Relevance ◽  
Cell Recovery ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Cell Counts ◽  
Latent Hiv ◽  
Hiv 1

ABSTRACT Follicular helper T (TFH) cells have been shown to support productive human immunodeficiency virus type 1 (HIV-1) replication and to serve as a key component of the latent viral reservoir. However, the viral characteristics of this latent reservoir and the clinical relevance of this reservoir remain unclear. In this study, we assessed the tropic composition of latent viruses from peripheral TFH (pTFH), non-TFH memory, and naive CD4+ T cells from individuals with HIV-1 infections on suppressive combined antiretroviral therapy (cART). X4-tropic latent HIV-1 was preferentially enriched in pTFH cells compared to levels in the other two subsets. Interestingly, the ratio of X4-tropic latent HIV-1 in pTFH cells not only was robustly and inversely correlated with blood CD4+ T cell counts across patients but also was prognostic of CD4+ T cell recovery in individuals on long-term cART. Moreover, patients with higher X4-tropic latent HIV-1 ratios in pTFH cells showed greater risks of opportunistic coinfections. These findings reveal the characteristics of latent HIV-1 in TFH cells and suggest that the ratio of X4-tropic latent HIV-1 in pTFH cells is a valuable indicator for disease progression and cART efficacy. IMPORTANCE TFH cells have been shown to harbor a significant amount of latent HIV-1; however, the viral characteristics of this reservoir and its clinical relevance remain largely unknown. In this study, we demonstrate that X4-tropic latent HIV-1 is preferentially enriched in pTFH cells, which also accurately reflects the viral tropism shift. The ratio of X4-tropic proviruses in pTFH cells but not in other memory CD4+ T cell subsets is inversely and closely correlated with blood CD4+ T cell counts and CD4+ T cell recovery rates with cART. Our data suggest that the ratio of X4-tropic provirus in peripheral TFH cells can be easily measured and reflects disease progression and treatment outcomes during cART.

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