scholarly journals Maternal Exposure Results in Long-Term Deoxynivalenol Persistence in Piglets’ Plasma and Modulates the Immune System

Toxins ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 615 ◽  
Author(s):  
Hana Štěpánová ◽  
Karolina Hlavová ◽  
Kamil Šťastný ◽  
Eduard Gopfert ◽  
Lenka Levá ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Γδ T Cells ◽  
High Sensitivity ◽  
Postnatal Period ◽  
Double Positive ◽  
Toxicological Effects ◽  
Immune Parameters ◽  
The Impact

Deoxynivalenol (DON)-contaminated feed represents a serious problem for pigs due to their high sensitivity to its toxicological effects. The aim of the present study was to evaluate the impact of intrauterine DON exposure on the immune system of piglets. Pure DON was intravenously administered to sows at the end of gestation (during the last 2–3 days of gestation, one dose of 300 µg per day). The plasma concentration of DON was analyzed using liquid chromatography combined with high-resolution Orbitrap-based mass spectrometry (LC–MS/MS (HR)) and selected immune parameters were monitored six times in piglets from birth to 18 weeks. DON was found in the plasma of 90% of newborn piglets at a mean concentration of 6.28 ng/mL and subsequently, at one, three, and seven weeks after birth with decreasing concentrations. Trace amounts were still present in the plasma 14 weeks after birth. Flow cytometry revealed a significant impact of DON on T lymphocyte subpopulations during the early postnatal period. Lower percentages of regulatory T cells, T helper lymphocytes, and their double positive CD4+CD8+ subset were followed by increased percentages of cytotoxic T lymphocytes and γδ T cells. The capacity to produce pro-inflammatory cytokines was also significantly lower after intrauterine DON exposure. In conclusion, this study revealed a long-term persistence of DON in the plasma of the piglets as a consequence of short-term intrauterine exposure, leading to altered immune parameters.

scholarly journals The analysis of the long-term impact of SARS-CoV-2 on the cellular immune system in individuals recovering from COVID-19 reveals a profound NKT cell impairment

2020 ◽  
Author(s):  
jia liu ◽  
Xuecheng Yang ◽  
Hua Wang ◽  
Ziwei Li ◽  
Hui Deng ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Annexin V ◽  
Double Positive ◽  
Peripheral Blood Mononuclear ◽  
Cellular Immune System ◽  
Cellular Immune

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects millions of people and killed hundred-thousands of individuals. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remained to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells in 49 COVID-19 convalescent individuals (CI) in comparison to 27 matched SARS-CoV-2 unexposed individuals (UI). Despite recovery from the disease for more than 2 months, CI showed significant decreases in frequencies of invariant NKT and NKT-like cells compared to UI. Concomitant with the decrease in NKT-like cells, an increase in the percentage of Annexin V and 7-AAD double positive NKT-like cells was detected, suggesting that the reduction in NKT-like cells results from cell death months after recovery. Significant increases in regulatory T cell frequencies, TIM-3 expression on CD4 and CD8 T cells, as well as PD-L1 expression on B cells were also observed in CI, while the cytotoxic potential of T cells and NKT-like cells, defined by GzmB expression, was significantly diminished. However, both CD4 and CD8 T cells of CI showed increased Ki67 expression and were fully capable to proliferate and produce effector cytokines upon TCR stimulation. Collectively, we provide the first comprehensive characterization of immune signatures in patients recovering from SARS-CoV-2 infection, suggesting that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease.

scholarly journals Immunomodulatory Effects of Dietary Phosphorus and Calcium in Two Strains of Laying Hens

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 129
Author(s):  
Tanja Hofmann ◽  
Sonja Schmucker ◽  
Vera Sommerfeld ◽  
Korinna Huber ◽  
Markus Rodehutscord ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Egg Production ◽  
Laying Hens ◽  
Animal Health ◽  
Negative Effects ◽  
Mineral Phosphorus ◽  
Immune Parameters ◽  
Dietary Phosphorus ◽  
The Impact

Insufficient nutrient supply can impair the immune system, which is important for animal health and welfare. Since chicken can partly hydrolyze phytate, which is the primary phosphorus storage in plant seeds, a reduction of mineral phosphorus in the diets could be an option for more sustainable egg production. Laying hens require high concentrations of calcium that might inhibit the function of endogenous enzymes for phytate hydrolyzation. The objective of this study was to characterize the impact of standard and reduced dietary phosphorus and calcium concentrations on the number and functionality of immune cells in the peripheral and gut-associated immune system in a white and brown laying hen strain. Reduced mineral phosphorus enhanced several immune parameters such as B cells in blood and IgA concentrations in bile in both strains, and peripheral monocytes and T cells in cecal tonsils in brown hens. Reduced calcium levels resulted in lower numbers of T cells in blood and cecal tonsils in both strains, suggesting negative effects on adaptive immunity. Differences between the two strains were found in almost all immune parameters. Results suggest a potentially beneficial effect of reduced dietary mineral phosphorus on the immune system that is dependent on the genetic background.

scholarly journals T Cells Limit Accumulation of Aggregate Pathology Following Intrastriatal Injection of α-Synuclein Fibrils

2021 ◽  
pp. 1-19
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

Molecular Bases for Pharmacotherapy of COVID -19

2021 ◽  
Vol 6 (5) ◽  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Mortality Rate ◽  
Large Scale ◽  
Tissue Injury ◽  
Diffuse Alveolar Damage ◽  
New Drugs ◽  
Patient Death ◽  
Double Positive ◽  
Host Cell Membrane

The most large-scale challenge aroused at the beginning of Y2020 was the global spread of the coronavirus disease 2019 (COVID-19), caused by a zoonotic beta-coronavirus. One year after we have nearly 270 thousand confirmed cases with mortality rate 1.3% in Georgia, and almost 120 billion confirmed cases with mortality rate 2.2% worldwide. As it is known, COVID-19 is triggered by coronavirus species 2 or SARS-CoV-2, which inters in the human body by binding to the angiotensin-converting enzyme 2 (ACE2) molecule on the host cell membrane via the viral spike protein and expresses complex pathological changes in many organs linked with vascular injuries. The most severe expression of this disease exposed by microscopic examination is bilateral diffuse alveolar damage with fibroblasts exudates, indicating Acute Respiratory Distress Syndrome (ARDS). Immune system plays crucial role in tissue damage. As clinical researches showed, the number of peripheral CD4+ and CD8 + T cells were significantly reduced, while their activity was hyper-expressed as evidenced by the high proportions of HLADR (CD4 3•47%) and CD38 (CD8 39•4%) double-positive fractions. Moreover, there was identified an amplified concentration of highly pro inflammatory CCR6+ Th17 in CD4 T cells. This date explains that severe tissue injury in later stages of COVID-19 is depend on the immune system abnormalities, but not on SARS-CoV-2 direct cell destruction. In the same time the scientists and doctors found out abnormalities in coagulation function in most of the severe COVID-19 patients, which were expressed in elevation of D-Dimer level and prolongation of prothrombin time, some of whom terminated in disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT) or fatal pulmonary thromboembolism (PTE). At the later stage in some severe patients it was identified thrombocytopenia as a result of excessive platelets consuming, which significantly affected on treatment and prognosis. More than 300 drugs are used for the treatment of COVID-19 worldwide. Now, the most popular treatments include Remdesivir, Hydroxychloroquine, Betamethasone, Tocilizumab, anti HIV drugs, and convalescent plasma. In the same time, WHO supports vaccines distribution for immunization. Currently, almost 8 vaccines are approved by different countries and more than 180 vaccines are under the clinical trails. Conclusion & Significance: Up till now it is challenging problem to combat SARS-CoV-2 with not well-defined origin and inexplicable biological characteristics as well as to control a pandemic of COVID-19 with such a high R0, a long incubation period and different disease outcomes. Unfortunately, we have limited understandings of particular mechanisms running to abnormal expression of immune system and coagulation processes. In the same time, we don’t have complete picture of vasculopathy leading to the tissue injury and patient death. Therefore, it is problematic to manage SARS-CoV-2 induced processes successfully using available drugs with no significant restoring effect on the organ damages in severe COVID-19 patients. So, we need new targets and new drugs for the prophylaxes and treatment of COVID-19 even we have vaccines available.

Peripheral Immunological Cells in Pregnant Women and their Change during Diabetes

2017 ◽  
Vol 125 (10) ◽  
pp. 677-683 ◽  
Author(s):  
Ulrike Friebe-Hoffmann ◽  
Linda Antony ◽  
Jan-Steffen Kruessel ◽  
Brigitte Pawlowski ◽  
Thomas Hoffmann
Keyword(s):  
T Cells ◽  
Gestational Diabetes ◽  
Pregnant Women ◽  
Immune Cell ◽  
Γδ T Cells ◽  
Complication Rates ◽  
And Shifts ◽  
The Impact ◽  
Pregnant Diabetic

AbstractDuring the last decades the incidence of diabetes has dramatically increased as well as the number of pregnant diabetic women. There is still missing data regarding patterns and shifts of immune cell populations due to pregnancy with or without diabetes. The study aimed to investigate the impact of pregnancy, type 1 diabetes (T1D) and gestational diabetes mellitus (GDM) on different immune cells in female. The number and proportion of CD3-, CD4-, CD8- and γδ T-cells as well as B-, NK-, NKT- and dendritic cells (DC) incl. rate of apoptosis was analyzed in peripheral blood samples from 24 non-pregnant women, 24 pregnant controls, 25 non-pregnant T1D, 18 women with GDM and 15 pregnant T1D (PT1D) women. Compared to healthy controls, healthy pregnant women had reduced numbers of lymphoid DC and γδ T-cells, while women with gestational diabetes presented with increased numbers of γδ T-cells. Pregnant women with T1D showed increased NKT cells and a decrease of NK cells compared to healthy pregnant or non-pregnant T1D women. Apoptosis of γδ T-cells in healthy pregnant women was found to be decreased in comparison to their non-pregnant controls while apoptosis of myeloid and lymphoid DC was increased in pregnant T1D in comparison to non-pregnant T1D. Those results may indicate that increased complication rates during diabetic pregnancies might be due to an impaired adaptation of the immune system.

Keep Your Brain Tissue Healthy

2021 ◽  
pp. 27-66
Author(s):  
Charles Alessi ◽  
Larry W. Chambers ◽  
Muir Gray
Keyword(s):  
Physical Activity ◽  
Immune System ◽  
Inflammatory Response ◽  
Stress Reduction ◽  
Indirect Effects ◽  
Cognitive Abilities ◽  
Direct And Indirect Effects ◽  
The Impact ◽  
The Brain

This chapter starts by advising how to reduce the impact of stress. When stress becomes long term, the immune system becomes less sensitive to cortisol, and since inflammation is partly regulated by this hormone, this decreased sensitivity heightens the inflammatory response and allows inflammation to get out of control, increasing our risk of many diseases. You can reduce your stress yourself through a variety of methods, including physical activity and mindfulness-based stress reduction. Adequate sleep is also a major factor that can improve cognitive abilities and reduce the risk of dementia, and this chapter outlines what we need to know about sleep cycles, insomnia, and sleep disordered breathing, and how to sleep more and sleep better. The chapter then covers how to protect your brain from over medication (polypharmacy). It finishes by discussing how to maintain and indeed increase your levels of physical activity, and how increasing physical activity has both direct and indirect effects on the brain.

scholarly journals Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Guillaume Carissimo ◽  
Weili Xu ◽  
Immanuel Kwok ◽  
Mohammad Yazid Abdad ◽  
Yi-Hao Chan ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Whole Blood ◽  
Roc Analysis ◽  
Γδ T Cells ◽  
High Sensitivity ◽  
The Novel ◽  
Cellular Mechanisms ◽  
Cell Counts ◽  
Novel Coronavirus

Abstract SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.

scholarly journals Vγ9Vδ2 T Cells: Can We Re-Purpose a Potent Anti-Infection Mechanism for Cancer Therapy?

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 829 ◽  
Author(s):  
Klaus-Peter Künkele ◽  
Daniela Wesch ◽  
Hans-Heinrich Oberg ◽  
Martin Aichinger ◽  
Verena Supper ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Therapy ◽  
Γδ T Cells ◽  
Host Cells ◽  
Advantages And Disadvantages ◽  
Therapeutic Concepts ◽  
Vγ9vδ2 T Cells ◽  
The Impact

Cancer therapies based on in vivo stimulation, or on adoptive T cell transfer of Vγ9Vδ2 T cells, have been tested in the past decades but have failed to provide consistent clinical efficacy. New, promising concepts such as γδ Chimeric Antigen Receptor (CAR) -T cells and γδ T-cell engagers are currently under preclinical evaluation. Since the impact of factors, such as the relatively low abundance of γδ T cells within tumor tissue is still under investigation, it remains to be shown whether these effector T cells can provide significant efficacy against solid tumors. Here, we highlight key learnings from the natural role of Vγ9Vδ2 T cells in the elimination of host cells bearing intracellular bacterial agents and we translate these into the setting of tumor therapy. We discuss the availability and relevance of preclinical models as well as currently available tools and knowledge from a drug development perspective. Finally, we compare advantages and disadvantages of existing therapeutic concepts and propose a role for Vγ9Vδ2 T cells in immune-oncology next to Cluster of Differentiation (CD) 3 activating therapies.

Multidimensional Flow Cytometric (MFC) Analysis of the Immune System of Multiple Myeloma (MM) Patients Achieving Long Term Disease Control

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 810-810
Author(s):  
Roberto J. Pessoa Magalhaes ◽  
María-Belén Vidriales ◽  
Bruno Paiva ◽  
Maria-Victoria Mateos ◽  
Norma C. Gutierrez ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Disease Control ◽  
B Cell ◽  
Nk Cells ◽  
Cell Populations ◽  
High Dose ◽  
Newly Diagnosed

Abstract Abstract 810FN2 Increasing evidence shows that a small fraction of MM patients (pts) treated with high-dose therapy followed by autologous stem cell transplantation achieve long-term remission. Interestingly, this is not restricted to pts in complete response (CR), since those that revert to a monoclonal gammopathy of undetermined significance (MGUS) profile may also achieve long-term remission, despite the persistence of residual myeloma plasma cells (PCs). These results suggest that in addition to the anti-myeloma therapy, other factors may play a role in the control of the disease. Herein, we used 8-color MFC for detailed characterization of the structural components of the immune system and hematopoietic precursor cells (HPC) in paired bone marrow (BM) and peripheral blood (PB) samples from 26 MM patients in long-term disease control (LTDC): 9 in continuous CR and 17 who reverted to an MGUS profile and that subsequently showed stable disease without treatment for ≥5 years (median of 9 years; range, 5–19). As controls, paired BM and PB samples from 23 newly-diagnosed MGUS and 16 MM pts, together with 10 healthy adults (HA), were studied in parallel. In all BM and PB samples the distribution of the major T- (CD4, CD8, Tregs and γδ), NK- (CD56dim and CD56bright) and B-cell subsets (Pro-B, Pre-B, naïve and memory), in addition to normal PCs, dendritic cell (DC) subsets (plasmacytoid, myeloid and monocytic), monocytes, and CD34+ HPC (myeloid and lymphoid), were studied. The percentage and absolute count of each cell population was analysed in the BM and PB, respectively. Comparison of the two groups of MM pts with LTDC (9 CR vs. 17 MGUS-like) showed similar (p>.05) cellular profiles in PB and BM, except for an increased number of BM and PB normal PCs in CR patients (P≤.04). Consequently, for all subsequent analyses, LTDC myeloma pts were pooled together. When compared to HA, patients with LTDC had increased numbers of CD8 T-cells and CD56dim NK-cells in both the BM and PB (p≤.03 and p≤.01, respectively). Despite this, the distribution of BM and PB CD4, CD8 and γδ T-cells among LTDC patients was similar (p>.05) to that of both newly-diagnosed MM and MGUS cases; in contrast, BM and PB Tregs were significantly decreased vs newly-diagnosed MM (P=.03) and MGUS (P=.04). Regarding B-cells and normal PCs, LTDC patients showed increased numbers of BM B-cell precursors (both Pro-B and Pre-B cells) and normal PCs vs. newly diagnosed MM (P≤.05), but not MGUS, together with increased numbers of naïve B-cells vs. both MM and MGUS pts (P≤.01); all such cell populations returned to levels similar (p>.05) to those of HA. As expected, this also included the number of CD34+ B-cell HPC which was increased among patients who achieved LTDC vs MM (p=.02), at levels similar (p>.05) to those of MGUS and HA. Regarding DC, LTDC patients showed normal DC numbers in PB (but with higher PB myeloid-DC numbers vs. MM; p=.02), in association with decreased numbers of plasmacytoid DC and increased monocytic-DC in the BM vs. HA (p≤.04). No differences were found for the numbers of BM and PB monocytes. In summary, here we investigated for the first time the immune cell profile of MM patients who achieve long-term disease control. Our results show that, as newly-diagnosed MM, patients that achieve long-term disease control also show increased numbers of cytotoxic T-cells and CD56dim NK-cells; however, in contrast to newly-diagnosed MM, among LTDC patients such increase is associated with lower numbers of T-regs and an almost complete recovery of the normal PC, B-cell precursor and naïve B-cell compartments both in BM and PB. Further investigations on the activation and functional status of these cell populations are warranted.MO (%)/SP (cels./μl)HA N= 10MGUS N= 23MM N= 16LTDC-MM N= 26T cells9.588110.6117313113711926    CD4+4.85004.6624^6*5085463    CD8+3.7∼216∼4.63865.32645.3431    TCR γδ.2426.3230.2428.3421    Treg.4137.4141^.54*38.3432NK cells.7∼87∼1.51982.11721.6212    CD56 dim.65∼79∼1.41922.21681.6202B cells2.81471.8104.97*68*1.9160    Pro B.11—.06—.02*—.07—    Pre B.6—.4—.08—.23—    Naive SP—80—57^—36*—118    Normal-PCS.18.9.11.7.008.72*.11.84DCs.3449.3653.6848.558    Monocytes2.22472.42853.43023.1315    m-DC SP—11—14—8*—12    MO-DC.11∼29.2036.434.2837    p-DC.2∼4.1.145.112.8.123.8CD34+.9∼1.46.61.1.261.4.431.4    Mie-HPC.8∼—.53—.26—.36—    Linfo-HPC.1—.07—.03*—.05—*p≤.05 LTDC vs MM: ^ p≤.05 LTDC vs MGUS; ∼ p≤.05 LTDC vs HA Disclosures: Paiva: Jansen-Cillag: Honoraria; Celgene: Honoraria. Martinez:Janssen: Honoraria; Celgene: Honoraria. Maiolino:Centocor Ortho Biotech Research & Development: Research Funding.

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