scholarly journals ROLE OF CYTOXIC T-LYMPHOCYTES IN THE PATHOGENESIS OF PRETERM BIRTH

2021 ◽  
Vol 23 (4) ◽  
pp. 859-864
Author(s):  
N. R. Radzhabova ◽  
N. Yu. Sotnikova ◽  
A. V. Kudryashova ◽  
N. Yu. Borzova ◽  
A. I. Malyshkina

Currently, the existence of a wide range of subpopulations of CD8+T-lymphocytes has been revealed, among which there are subpopulations of naive and effector cells, as well as memory cells. CD8+T-lymphocytes are thought to be a population of lymphocytes with high cytotoxic activity, which is of extreme importance during pregnancy. Given that each subpopulation is characterized by a set of produced mediators, surface and intracellular markers, we can assume their role in the pathogenesis of preterm birth. This determined the need to investigate the role of naive cells, effector cells, and memory cells in the development of spontaneous preterm birth. Data on the content of naive CD8+-lymphocytes in the peripheral blood of women with threatened preterm birth are practically absent. It was found that the infiltration of CD8+-lymphocytes in the area of uteroplacental contact was associated with the development of timely delivery. Chronic chorioamnionitis is the most common condition in idiopathic preterm birth and is characterized by the infiltration of maternal CD8+Tcells into the chorioamniotic membranes. Currently, it is believed that chronic inflammatory lesions of the placenta represent maternal antifetal rejection. This led to the study of the role of these cells in the pathogenesis of preterm birth. Purpose. To establish a possible pathogenetic mechanism of preterm birth in women with threatened preterm birth on the basis of the revealed features of differentiation and functional activity of CD8+- lymphocytes at the systemic levelMaterials and methods. The survey of women was carried out on the basis of the Federal State Budgetary Institution “V. Gorodkov Ivanovo Research Institute of Maternity and Childhood” of the Ministry of Health of the Russian Federation. A total of 126 women were examined, which were retrospectively divided into 2 main groups – women with threatened preterm birth(n = 68), which was divided into 2 subgroups – with the outcome of pregnancy preterm birth (n = 30) and timely delivery (n = 38). The control group included 58 women with uncomplicated pregnancy and who gave birth on time. In the CD8+-lymphocyte population, the content of central – Tcm (CD45RACD62L+), preterminally differentiated-Tem (CD45RACD62L- ) and terminally differentiated-Temra (CD45RA+CD62L- ) memory cells was determined. In all memory cell populations, the content of cells producing Granzyme B intracellularly was determined. The studies were performed using monoclonal antibodies (mAT) by flow cytometry on a FACSCanto II cytometer using the FACSDiva software (Becton Dickinson, USA).The analysis of the features of the relative content of CD8+-lymphocytes in the main group of women, depending on the outcome of pregnancy, was carried out. When comparing patients with a clinic of threatened preterm birth, whose pregnancy ended prematurely, a higher content of CD8+-lymphocytes was revealed than in group c of women who gave birth in a timely manner, which indicates a high stimulation of cytotoxic T-lymphocytes in this group of women. With threatening preterm birth, there is an increase in the content of naive CD8+-lymphocytes in the peripheral blood. Data on the content of naive CD8+-lymphocytes in the peripheral blood of women with threatened preterm birth are practically absent. The increase in CD8+Tn levels is more pronounced in the subgroup of women with a favorable pregnancy outcome. Given this fact, it can be assumed that in women with preterm birth, a lower CD8+Tn is associated with their increased differentiation into effector T-lymphocytes with their subsequent migration to the placental zone. This process could determine the observed decrease in the level of terminally differentiated granzyme-producing CD8+-lymphocytes in a subgroup of women with a pregnancy outcome of preterm birth, which coincided with the literature data. 

2020 ◽  
Vol 66 (6) ◽  
pp. 477-484
Author(s):  
L.V. Krechetova ◽  
L.V. Vanko ◽  
V.V. Vtorushina ◽  
M.A. Nikolaeva ◽  
E.V. Inviyaeva ◽  
...  

The aim of this work was to characterize phenotypically peripheral blood T- and NK lymphocytes expressing an early marker of activation, CD69, and assess the significance of CD69 expression for predicting pregnancy outcome in women with idiopathic reccurent pregnancy loss (IRP) before and after immunocytotherapy (ICT). The study group consisted of 36 patients with IRP who became pregnant after pre-gestational allimmunization, in 30 patients the pregnancy was prolonged to the full term and ended with the birth of a viable baby, in 6 — it was terminated before 12 weeks of gestation. In the control group, 15 fertile women outside pregnancy and 11 women at 12 weeks of physiological pregnancy were examined. Assessment of the CD69 expression in women with prolonged pregnancy revealed the absence of significant differences with the control group in the content and proportion of activated lymphocytes (CD69+). In women with aborted pregnancy after pre-gestational ICT, an increase in the number of almost all analyzed lymphocyte subpopulations responding to the activation stimulus, with a clear tendency to increase the proportion of activated T- but not NK-lymphocytes was found. At 5-6 weeks, the proportion of activated lymphocytes among a subpopulation of cytotoxic T-lymphocytes (CD3+CD8+/CD3+CD8+CD69+) in these women was significantly higher than in women with prolonged pregnancy, which confirms the leading role of effector cytotoxic T-lymphocytes in rejection reactions. Thus, the studies showed the promise of evaluating the expression of the early activation marker CD69 as an additional laboratory criterion for the personable appointment of immunocytotherapy to women with a common reccurent pregnancy loss.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Clara Saad Menezes ◽  
Alicia Dudy Müller Veiga ◽  
Thais Martins de Lima ◽  
Suely Kunimi Kubo Ariga ◽  
Hermes Vieira Barbeiro ◽  
...  

AbstractThe role of innate immunity in COVID-19 is not completely understood. Therefore, this study explored the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the expression of Pattern Recognition Receptors (PRRs) in peripheral blood cells and their correlated cytokines. Seventy-nine patients with severe COVID-19 on admission, according to World Health Organization (WHO) classification, were divided into two groups: patients who needed mechanical ventilation and/or deceased (SEVERE, n = 50) and patients who used supplementary oxygen but not mechanical ventilation and survived (MILD, n = 29); a control group (CONTROL, n = 17) was also enrolled. In the peripheral blood, gene expression (mRNA) of Toll-like receptors (TLRs) 3, 4, 7, 8, and 9, retinoic-acid inducible gene I (RIGI), NOD-like receptor family pyrin domain containing 3 (NLRP3), interferon alpha (IFN-α), interferon beta (IFN-β), interferon gamma (IFN-γ), interferon lambda (IFN-λ), pro-interleukin(IL)-1β (pro-IL-1β), and IL-18 was determined on admission, between 5–9 days, and between 10–15 days. Circulating cytokines in plasma were also measured. When compared to the COVID-19 MILD group, the COVID-19 SEVERE group had lower expression of TLR3 and overexpression of TLR4.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yixuan Liu ◽  
Suhong Xie ◽  
Lei Li ◽  
Yanhui Si ◽  
Weiwei Zhang ◽  
...  

Abstract Background This study investigates the effect of autologous bone marrow transfusion (BMT) on the reconstruction of both bone marrow and the immune system in patients with AIDS-related lymphoma (ARL). Methods A total of 32 patients with ARL participated in this study. Among them, 16 participants were treated with conventional surgery and chemotherapy (control group) and the remaining 16 patients were treated with chemotherapy followed by autologous bone marrow transfusion via a mesenteric vein (8 patients, ABM-MVI group) or a peripheral vein (8 patients, ABM-PI group). Subsequently, peripheral blood and lymphocyte data subsets were detected and documented in all patients. Results Before chemotherapy, no significant difference in indicators was observed between three groups of ARL patients. Unexpectedly, 2 weeks after the end of 6 courses of chemotherapy, the ABM-MVI group, and the ABM-PI group yielded an increased level of CD8+T lymphocytes, white blood cells (WBC), and platelet (PLT) in peripheral blood in comparison to the control group. Notably, the number of CD4+T lymphocytes in the ABM-PI group was significantly higher than that in the other two groups. Additionally, no significant difference in haemoglobin levels was observed before and after chemotherapy in both the ABM-MVI and ABM-PI groups, while haemoglobin levels in the control group decreased significantly following chemotherapy. Conclusions Autologous bone marrow transfusion after chemotherapy can promote the reconstruction of both bone marrow and the immune system. There was no significant difference in bone marrow recovery and reconstruction between the mesenteric vein transfusion group and the peripheral vein transfusion group.


Medicina ◽  
2007 ◽  
Vol 43 (1) ◽  
pp. 60 ◽  
Author(s):  
Vilma Jurkštienė ◽  
Anatolijus Kondrotas ◽  
Egidijus Kėvelaitis

The aim of the study was to investigate the immunostimulatory properties of bigroot geranium. Material and methods. Possible nonspecific characteristics of bigroot geranium were evaluated by the total leukocyte count in the peripheral blood, and qualitative changes of blood were assessed using Shilling’s formula by evaluating changes in lymphocyte counts. In addition, we also studied changes in the counts of Tcell precursors in the thymus and B lymphocytes in the spleen. Ethanol extract of the leaves of bigroot geranium was produced at the Department of Food Technology, Kaunas University of Technology. Studies were performed on mice Bl 57 (n=21). The control group (n=7) received distilled water at a dose of 1 mL/day. The second and third groups received 1% and 10% extract of bigroot geranium, respectively, as a food supplement. Changes in cell counts were investigated after 4 weeks following the initiation of the trial. Results. After a 4-week administration of 1% extract of bigroot geranium (1 mL/day) (mice group, n=7), leukocyte count in the peripheral blood increased to 6.1×109 cells/L, and lymphocyte count – to 70%, but changes were not statistically significant. The other case group of mice (n=7) received 10% extract of bigroot geranium for 4 weeks at a dose of 1 mL/day. In this group, leukocyte count in the peripheral blood increased statistically significantly from 4.4×109 cells/L to 7.2×109 cells/L (p<0.01), and lymphocyte percentage – from 52% to 80% (p<0.001), as compared to control. Thymocyte (T lymphocytes) counts in thymus and splenocyte (B lymphocytes) counts in the spleen showed a tendency to increase after the administration of 1% and 10% extracts. After a 4-week administration of 1% extract of bigroot geranium, thymocyte and splenocyte counts increased from 0.342×106 cells to 0.372×106 cells per mg of tissue and from 0.395×106 cells to 0.405×106 cells per mg of tissue, respectively, as compared to control group (p>0.1). After the administration of 10% extract of bigroot geranium, thymocyte count increased to 0.488×106 cells per mg of tissue (p<0.01), and splenocyte count – to 0.504×106 cells per mg of tissue (p<0.01). Conclusion. The extracts of the leaves of bigroot geranium increased leukocyte count and lymphocyte percentage in the peripheral blood, and after a 4-week administration of 10% extract of bigroot geranium, a statistically significant increase in the counts of T lymphocytes (in the thymus) and B lymphocytes (in the spleen) was observed. The immunostimulatory effect depends on the dose of the extract.


1981 ◽  
Vol 90 (2) ◽  
pp. 145-150 ◽  
Author(s):  
K. H. HARRIS ◽  
B. D. MURPHY

The role of prolactin in the maintenance of the corpus luteum of pseudopregnancy was studied in the golden hamster. Nine groups of seven to fourteen animals each received 1 mg bromocriptine at 11.00 h on days 1, 2 or 3 of pseudopregnancy (three groups for each day). On each day of treatment with bromocriptine, one group of hamsters was injected with bovine prolactin 4 h before bromocriptine, and one group received prolactin 4 h before bromocriptine for three consecutive days following treatment with bromocriptine. One group received bromocriptine only. These nine groups were compared with a control group of animals given 0·85% saline instead of bromocriptine and prolactin. Peripheral blood samples were taken from all hamsters at 11.00 h on days 3, 4, 5 and 6 of pseudopregnancy and plasma levels of progesterone were determined by radioimmunoassay. Luteolysis, indicated by a decline in progesterone level by 24 or 48 h after treatment with bromocriptine, occurred in all hamsters given bromocriptine alone, whether it was administered on day 1, 2 or 3. Pretreatment with a single dose of prolactin did not mitigate the bromocriptine-induced fall in progesterone. In the majority of cases, pretreatment with prolactin plus daily doses of prolactin maintained the progesterone at levels not different from saline-treated hamsters. These data suggest that prolactin is a necessary luteotrophin during early pseudopregnancy without which luteolysis ensues.


2021 ◽  
Vol 18 (4) ◽  
pp. 863-868
Author(s):  
Wanfeng Wu ◽  
Chengting Jiang ◽  
Cheng Cheng ◽  
Yihang Sun ◽  
Ning Luo ◽  
...  

Purpose: To study the combined effects of tenofovir and interferon α1b on viral load and peripheral blood regulatory T cell concentrations of chronic hepatitis B (CHB) subjects. Methods: Patients with chronic hepatitis B (86 cases) were randomly assigned to two groups: control group and study group. In control subjects, tenofovir was given orally (300 mg/kg bwt/day). In addition to tenofovir, the study group received interferon α1b injection intramuscularly at a dose of 50 μg/kg thrice a week. Liver function, serum hepatitis B viral (HBV) load, and serum levels of peripheral blood regulatory T-lymphocytes were determined. Clinical effectiveness and adverse reactions in both groups were also assessed. Results: After treatment, total effectiveness was higher in the study group (86.04 %) than in control patients (62.79 %) (p < 0.05). Serum aspartate transaminase (AST), alanine aminotransferase (ALT) and total bilirubin (TBIL) significantly decreased in the study group, relative to control, but HBV DNAnegative, HbeAg-negative and HbsAg-negative cells were markedly higher in patients in the study group (p < 0.05). Moreover, there were higher CD4+ T and CD8+ T counts, and CD4+ T/CD8+ T ratio in study subjects than in control subjects (p < 0.05). Conclusion: The combination of tenofovir with interferon α1b effectively improves liver functions in patients with CHB, reduces viral load, and exerts anti-HBV effect by regulating the levels of peripheral blood T-lymphocytes.


Author(s):  
Darya B. Nizheharodava ◽  
Marina M. Zafranskaya ◽  
Eugenii I. Kvasyuk ◽  
Aliaksei G. Sysa

Taking into account the special role of oxidative stress that increases during cancer chemotherapy, the effect of the antioxidant emoxipine on peripheral blood mononuclears was studied under conditions that simulate the cytotoxic effects of antimetabolites of a number of modified cytidine nucleosides in relation to the tumor cell line K562. Lymphoid cells were also a source for subsequent modelling of the immune response to the cancer. It was found that neither the modified nucleosides themselves nor their combination with emoxipine caused changes in IL-2-stimulated cytotoxicity of lymphoid cells in relation to K562 tumor cell line. A study of the expression of the CD107a marker showed a significant stimulating effect of 1 µmol/L of citarabine on the activation of subpopulations of T-lymphocytes (CD3+ ) and cytotoxic T-lymphocytes (CD3+ CD8+ ).


2021 ◽  
Vol 67 (6) ◽  
pp. 39-49
Author(s):  
M. A. Dudina ◽  
S. A. Dogadin ◽  
A. A. Savchenko ◽  
V. D. Belenyuk

BACKGROUND: Effective control of autoimmune inflammation in Graves’ disease determines necessity to study the T helper (Th) and cytotoxic T-lymphocytes dysfunction, as well as the level of regulatory T-cells (Treg) activation in patients with Graves’ disease on thyrostatic medication, which will clarify the immunomodulatory effects of long-term thiamazole treatment serve as targets for more specific therapies.AIM: To study the phenotypic composition of T-lymphocytes in the peripheral blood of patients with Graves’ disease to assess the direction of immune response depending on thimazole-induced euthyroidism duration.MATERIALS AND METHODS: A single-center, cohort, continuous, open-label, controlled trial was conducted to assess the phenotypic composition of T-lymphocytes in peripheral blood in women with Graves’ disease on long-term thiamazole treatment. The phenotypic composition of T-lymphocytes was determined by flow cytometry using direct immunofluorescence with conjugated FITC monoclonal antibodies depending on the duration of thimazole-induced euthyroidism of long-term thiamazole treatment.RESULTS: The study included 135 women with Graves’ disease, mean age 43.09±12.81 years, 120 (88.91%) with a relapse of the disease and 15 (11.09%) with newly diagnosed hyperthyroidism. An increase of activated CD3+CD4+CD25+ was found in patients with Graves’ disease with a duration of thimazole-induced euthyroidism 5–8 months and 9–12 months, respectively, Me=0.94 (0.48–1.45), p=0.020) and Me=0.95 (0.41–1.80), p=0.025), in control group — Me=0.12 (0.03–0.68). Compared to the control an increase of CD4+CD25+CD127Low (Treg) was found in patients with a duration of thimazole-induced euthyroidism 5–8 and 9–12 months. The content of Treg in peripheral blood in Graves’ disease patients with a duration of thimazole-induced euthyroidism more than 12 months decreases, but remains elevated relative to the control.CONCLUSION: In patients with Graves’ disease with a duration of thimazole-induced euthyroidism 5–8 months and 9–12 months the level of Treg has been increased. The increase of activated Th (CD3+CD4+CD25+) persists independently of thimazole-induced euthyroidism. In patients with Graves’ disease with a duration of thimazole-induced euthyroidism for more than 12 months, there is a compensatory increase in regulatory T-lymphocyte, and the total number of T-helpers is restored to the control.


2019 ◽  
Vol 9 (3-4) ◽  
pp. 600-606
Author(s):  
Nikolay Nikolaevich Ilyinskikh ◽  
Ekaterina Nikolaevna Ilyinskikh ◽  
Evgenia Vladimirovna Zamyatina ◽  
Svetoslava Vyacheslavovna Lee

Aim of this study was to study the dynamics of the frequency of cytokinesis-blocked T-lymphocytes with micronuclei in peripheral blood and the frequency of buccal micronucleated epithelium cells for a period of half a year in patients with acute tick-borne encephalitis, depending on burden of active and inactive variants of glutathione-S-transferase genes (GSTM1 and GSTT1) in the patient's genotype. We carried out micronucleus assay in immunocompetent and non-immunocompetent cells in 54 patients with acute tick-borne encephalitis and 35 healthy persons (control) residing in the Tomsk and Tyumen regions. To analyze the frequency of cytokinesis-blocked micronucleated T-lymphocytes was used venous peripheral blood as material for phytohemagglutinin-stimulated cultures, and to study the frequency of buccal micronucleated cells, samples of the buccal mucous membrane epithelial cells were obtained. To carried out both techniques of micronucleus assay, cytological preparations were prepared, which were stained using the Giemsa or Felgen methods. The material for the study was obtained repeatedly during admission of patients to treatment, and also after 1 week, 1, 3 and 6 months.  Polymerase chain reaction was used to analyze the alleles of the GSTM1 and GSTT1 genes. As a result of this analysis was found a significant increase in the frequency of micronucleated cells in tick-borne encephalitis patients compared with the control group. In addition, the frequency of cytokinesis-blocked micronucleated T-lymphocytes was increased significantly higher than the one of micronucleated buccal cells. The most significant and prolonged increase in the frequency of micronucleated cells was associated with the mutant inactive variants of the genes GSTM1 (0/0) and GSTT1 (0/0). In the patients with burden the inactive forms of these genes, the cytogenetic instability of the cytokinesis-blocked blood T-lymphocytes could persist for up to six months. In case of buccal cells, the frequency of micronucleated cells was close to the one in the control group as early as 1-3 months after a course of treatment. Conclusion. It was found that the most increased and prolonged frequency of cytogenetically instable cells persisted in cytokinesis-blocked T-lymphocytes of peripheral blood of patients with tick-borne encephalitis who were carriers of the genotype with inactive variants of  both GSTM1 (0/0) and GSTT1 (0/0 ) glutathione-S-transferase genes.


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