scholarly journals Neuroinflammation is associated with infiltration of T cells in Lewy body disease and ɑ-synuclein transgenic models.

2020 ◽  
Author(s):  
Michiyo Iba ◽  
Changyoun Kim ◽  
Michelle Sallin ◽  
Somin Kwon ◽  
Anjali Verma ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Cells ◽  
Flow Cytometric Analysis ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Immunohistochemical Analysis ◽  
Peripheral Immune System ◽  
Adaptive Immune Cells ◽  
Close Proximity

Abstract Background: ɑ-synuclein (ɑ-syn) is a presynaptic protein which progressively accumulates in neuronal and non-neuronal cells in neurodegenerative diseases such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy. Recent evidence suggests that aberrant immune activation may be involved in neurodegeneration in PD/DLB. While previous studies have often focused on the microglial responses, less is known about the role of the peripheral immune system in these disorders.Methods: To understand the involvement of the peripheral immune system in PD/DLB, we evaluated T cell populations in the brains of ɑ-syn transgenic (tg) mice (eg: Thy1 promoter line 61) and DLB patients.Results: Immunohistochemical analysis showed perivascular and parenchymal infiltration by CD3+/CD4+ helper T cells, but not cytotoxic T cells (CD3+/CD8+) or B cells (CD20+), in the neocortex, hippocampus, and striatum of ɑ-syn tg mice. CD3+ cells were found in close proximity to the processes of activated astroglia, particularly in areas of the brain with significant astrogliosis, microgliosis, and pro-inflammatory cytokines. In addition, a subset of CD3+ cells co-expressed interferon γ. Flow cytometric analysis of immune cells revealed that CD1d+ T cells were also increased in the brains of ɑ-syn tg mice and matched an expression profile consistent with natural killer T cells. In post-mortem DLB brains, we similarly detected CD3+ T cells that expressed CD4+ or CD1d+ in close proximity with blood vessels.Conclusion: These results suggest that infiltrating adaptive immune cells play an important role in neuroinflammation and neurodegeneration in synucleinopathies and that modulating peripheral T cells may be a viable therapeutic strategy for PD/DLB.

scholarly journals The impact of body mass index on adaptive immune cells in the human bone marrow

2020 ◽  
Author(s):  
Luca Pangrazzi ◽  
Erin Naismith ◽  
Carina Miggitsch ◽  
Jose’ Antonio Carmona Arana ◽  
Michael Keller ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Bone Marrow ◽  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Immune Cells ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Abstract Background. Obesity has been associated with chronic inflammation and oxidative stress. Both conditions play a determinant role in the pathogenesis of age-related diseases, such as immunosenescence. Adipose tissue can modulate the function of the immune system with the secretion of molecules influencing the phenotype of immune cells. The importance of the bone marrow (BM) in the maintenance of antigen-experienced adaptive immune cells has been documented in mice. Recently, some groups have investigated the survival of effector/memory T cells in the human BM. Despite this, whether high body mass index (BMI) may affect immune cells in the BM and the production of molecules supporting the maintenance of these cells it is unknown.Methods. Using flow cytometry, the frequency and the phenotype of immune cell populations were measured in paired BM and PB samples obtained from persons with different BMI. Furthermore, the expression of BM cytokines was assessed. The influence of cytomegalovirus (CMV) on T cell subsets was additionally considered, dividing the donors into the CMV- and CMV+ groups.Results. Our study suggests that increased BMI may affect both the maintenance and the phenotype of adaptive immune cells in the BM. While the BM levels of IL-15 and IL-6, supporting the survival of highly differentiated T cells, and oxygen radicals increased in overweight persons, the production of IFNγ and TNF by CD8+ T cells was reduced. In addition, the frequency of B cells and CD4+ T cells positively correlated with BMI in the BM of CMV- persons. Finally, the frequency of several T cell subsets, and the expression of senescence/exhaustion markers within these subpopulations, were affected by BMI. In particular, the levels of bona fide memory T cells may be reduced in overweight persons.Conclusion. Our work suggests that, in addition to aging and CMV, obesity may represent an additional risk factor for immunosenescence in adaptive immune cells. Metabolic interventions may help in improving the fitness of the immune system in the elderly.

Body mass index affects adaptive immune cells in the human bone marrow

2020 ◽  
Author(s):  
Luca Pangrazzi ◽  
Erin Naismith ◽  
Carina Miggitsch ◽  
Jose’ Antonio Carmona Arana ◽  
Michael Keller ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Bone Marrow ◽  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Body Mass ◽  
Immune Cells ◽  
T Cell Subsets ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Abstract Background. Obesity has been associated with chronic inflammation and oxidative stress. Both conditions play a determinant role in the pathogenesis of age-related diseases, such as immunosenescence. Adipose tissue can modulate the function of the immune system with the secretion of molecules influencing the phenotype of immune cells. Recently, the importance of the bone marrow (BM) in the maintenance of antigen-experienced adaptive immune cells has been documented. Despite this, whether high body mass index (BMI) may affect immune cells in the BM and the production of molecules supporting the maintenance of these cells it is unknown. Methods. Using flow cytometry, the frequency and the phenotype of immune cell populations were measured in paired BM and PB samples obtained from persons with different BMI. Furthermore, the expression of BM cytokines was assessed. The influence of cytomegalovirus (CMV) on T cell subsets was additionally considered, dividing the donors into the CMV - and CMV + groups. Results. Our study suggests that increased BMI may affect both the maintenance and the phenotype of adaptive immune cells in the BM. While the BM levels of IL-15 and IL-6, supporting the survival of highly differentiated T cells, and oxygen radicals increased in overweight persons, the production of IFNγ and TNF by CD8 + T cells was reduced. In addition, the frequency of B cells and CD4 + T cells positively correlated with BMI in the BM of CMV - persons. Finally, the frequency of several T cell subsets, and the expression of senescence/exhaustion markers within these subpopulations, were affected by BMI. In particular, the levels of bona fide memory T cells may be reduced in overweight persons. Conclusion. Our work suggests that obesity may represent an independent risk factor supporting immunosenescence, in addition to aging and CMV. Metabolic interventions may help in improving the fitness of the immune system in the elderly.

scholarly journals Immune Vulnerability of Infants to Tuberculosis

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Koen Vanden Driessche ◽  
Alexander Persson ◽  
Ben J. Marais ◽  
Pamela J. Fink ◽  
Kevin B. Urdahl
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Immune System ◽  
Immune Cells ◽  
Active Tuberculosis ◽  
Age Group ◽  
Older Children ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Disseminated Disease

One of the challenges faced by the infant immune system is learning to distinguish the myriad of foreign but nonthreatening antigens encountered from those expressed by true pathogens. This balance is reflected in the diminished production of proinflammatory cytokines by both innate and adaptive immune cells in the infant. A downside of this bias is that several factors critical for controllingMycobacterium tuberculosisinfection are significantly restricted in infants, including TNF, IL-1, and IL-12. Furthermore, infant T cells are inherently less capable of differentiating into IFN-γ-producing T cells. As a result, infected infants are 5–10 times more likely than adults to develop active tuberculosis (TB) and have higher rates of severe disseminated disease, including miliary TB and meningitis. Infant TB is a fundamentally different disease than TB in immune competent adults. Immunotherapeutics, therefore, should be specifically evaluated in infants before they are routinely employed to treat TB in this age group. Modalities aimed at reducing inflammation, which may be beneficial for adjunctive therapy of some forms of TB in older children and adults, may be of no benefit or even harmful in infants who manifest much less inflammatory disease.

scholarly journals Lamin A/C and the Immune System: One Intermediate Filament, Many Faces

2020 ◽  
Vol 21 (17) ◽  
pp. 6109
Author(s):  
Angela Saez ◽  
Beatriz Herrero-Fernandez ◽  
Raquel Gomez-Bris ◽  
Beatriz Somovilla-Crespo ◽  
Cristina Rius ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Adaptive Immunity ◽  
Immune Cells ◽  
Cell Cycle Progression ◽  
Cell Types ◽  
Lamin A ◽  
Nuclear Mechanics ◽  
Adaptive Immune Cells ◽  
C Proteins

Nuclear envelope lamin A/C proteins are a major component of the mammalian nuclear lamina, a dense fibrous protein meshwork located in the nuclear interior. Lamin A/C proteins regulate nuclear mechanics and structure and control cellular signaling, gene transcription, epigenetic regulation, cell cycle progression, cell differentiation, and cell migration. The immune system is composed of the innate and adaptive branches. Innate immunity is mediated by myeloid cells such as neutrophils, macrophages, and dendritic cells. These cells produce a rapid and nonspecific response through phagocytosis, cytokine production, and complement activation, as well as activating adaptive immunity. Specific adaptive immunity is activated by antigen presentation by antigen presenting cells (APCs) and the cytokine microenvironment, and is mainly mediated by the cellular functions of T cells and the production of antibodies by B cells. Unlike most cell types, immune cells regulate their lamin A/C protein expression relatively rapidly to exert their functions, with expression increasing in macrophages, reducing in neutrophils, and increasing transiently in T cells. In this review, we discuss and summarize studies that have addressed the role played by lamin A/C in the functions of innate and adaptive immune cells in the context of human inflammatory and autoimmune diseases, pathogen infections, and cancer.

scholarly journals The impact of body mass index on adaptive immune cells in the human bone marrow

2020 ◽  
Author(s):  
Luca Pangrazzi ◽  
Erin Naismith ◽  
Carina Miggitsch ◽  
Jose’ Antonio Carmona Arana ◽  
Michael Keller ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Bone Marrow ◽  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Immune Cells ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

Abstract Background. Obesity has been associated with chronic inflammation and oxidative stress. Both conditions play a determinant role in the pathogenesis of age-related diseases, such as immunosenescence. Adipose tissue can modulate the function of the immune system with the secretion of molecules influencing the phenotype of immune cells. The importance of the bone marrow (BM) in the maintenance of antigen-experienced adaptive immune cells has been documented in mice. Recently, some groups have investigated the survival of effector/memory T cells in the human BM. Despite this, whether high body mass index (BMI) may affect immune cells in the BM and the production of molecules supporting the maintenance of these cells it is unknown.Methods. Using flow cytometry, the frequency and the phenotype of immune cell populations were measured in paired BM and PB samples obtained from persons with different BMI. Furthermore, the expression of BM cytokines was assessed. The influence of cytomegalovirus (CMV) on T cell subsets was additionally considered, dividing the donors into the CMV- and CMV+ groups.Results. Our study suggests that increased BMI may affect both the maintenance and the phenotype of adaptive immune cells in the BM. While the BM levels of IL-15 and IL-6, supporting the survival of highly differentiated T cells, and oxygen radicals increased in overweight persons, the production of IFNγ and TNF by CD8+ T cells was reduced. In addition, the frequency of B cells and CD4+ T cells positively correlated with BMI in the BM of CMV- persons. Finally, the frequency of several T cell subsets, and the expression of senescence/exhaustion markers within these subpopulations, were affected by BMI. In particular, the levels of bona fide memory T cells may be reduced in overweight persons.Conclusion. Our work suggests that, in addition to aging and CMV, obesity may represent an additional risk factor for immunosenescence in adaptive immune cells. Metabolic interventions may help in improving the fitness of the immune system in the elderly.

scholarly journals Persistent SARS-CoV-2 presence is companied with defects in adaptive immune system in non-severe COVID-19 patients

2020 ◽  
Author(s):  
Bing Liu ◽  
Junyan Han ◽  
Xiaohuan Cheng ◽  
Long Yu ◽  
Li Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Immune Cells ◽  
Healthy Subjects ◽  
Laboratory Data ◽  
Adaptive Immune System ◽  
Lymphocyte Subpopulations ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

AbstractBackgroundCOVID-19 has been widely spreading. We aim to examine adaptive immune cells in non-severe patients with persistent SARS-CoV-2 shedding.Methods37 non-severe patients with persistent SARS-CoV-2 presence transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to PP (persistently positive) group, which was further allocated to PPP group (n=19) and PPN group (n=18), according to their testing results after 7 days (N=negative). Epidemiological, demographic, clinical and laboratory data were collected and analyzed. Data from age- and sex-matched non-severe patients at disease onset (PA [positive on admission] patients, n=37), and lymphocyte subpopulation measurements from matched 54 healthy subjects were extracted for comparison.ResultsCompared with PA patients, PP patients had much improved laboratory findings, including WBCs, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, albumin, AST, CRP, SAA, and IL-6. The absolute numbers of CD3+ T cells, CD4+ T cells, and NK cells were significantly higher in PP group than that in PA group, and were comparable to that in healthy controls. PPP subgroup had markedly reduced B cells and T cells compared to PPN group and healthy subjects. Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative.ConclusionPersistent SARS-CoV-2 presence in non-severe COVID-19 patients is associated with reduced numbers of adaptive immune cells. Monitoring lymphocyte subpopulations could be clinically meaningful in identifying fully recovered COVID-19 patients.SummaryDefects in adaptive immune system, including reduced T cells and B cells, were frequently observed in non-severe COVID-19 patients with persistent SARS-CoV-2 shedding. Assessment of immune system could be clinically relevant for discharge management.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals Hyperthermia by near infrared radiation induced immune cells activation and infiltration in breast tumor

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wan Fatin Amira Wan Mohd Zawawi ◽  
M. H. Hibma ◽  
M. I. Salim ◽  
K. Jemon
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Side Effects ◽  
Immune Cells ◽  
Infrared Radiation ◽  
Near Infrared ◽  
Tumor Regression ◽  
Immunohistochemical Analysis ◽  
Therapeutic Effects ◽  
Near Infrared Radiation

AbstractBreast cancer is the most common cancer that causes death in women. Conventional therapies, including surgery and chemotherapy, have different therapeutic effects and are commonly associated with risks and side effects. Near infrared radiation is a technique with few side effects that is used for local hyperthermia, typically as an adjuvant to other cancer therapies. The understanding of the use of near NIR as a monotherapy, and its effects on the immune cells activation and infiltration, are limited. In this study, we investigate the effects of HT treatment using NIR on tumor regression and on the immune cells and molecules in breast tumors. Results from this study demonstrated that local HT by NIR at 43 °C reduced tumor progression and significantly increased the median survival of tumor-bearing mice. Immunohistochemical analysis revealed a significant reduction in cells proliferation in treated tumor, which was accompanied by an abundance of heat shock protein 70 (Hsp70). Increased numbers of activated dendritic cells were observed in the draining lymph nodes of the mice, along with infiltration of T cells, NK cells and B cells into the tumor. In contrast, tumor-infiltrated regulatory T cells were largely diminished from the tumor. In addition, higher IFN-γ and IL-2 secretion was observed in tumor of treated mice. Overall, results from this present study extends the understanding of using local HT by NIR to stimulate a favourable immune response against breast cancer.

Physical plasma and leukocytes – immune or reactive?

2018 ◽  
Vol 400 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Sander Bekeschus ◽  
Christian Seebauer ◽  
Kristian Wende ◽  
Anke Schmidt
Keyword(s):  
Wound Healing ◽  
Immune System ◽  
Plasma Treatment ◽  
Immune Cells ◽  
The Body ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Physical Plasma

AbstractLeukocytes are professionals in recognizing and removing pathogenic or unwanted material. They are present in virtually all tissues, and highly motile to enter or leave specific sites throughout the body. Less than a decade ago, physical plasmas entered the field of medicine to deliver their delicate mix of reactive species and other physical agents for mainly dermatological or oncological therapy. Plasma treatment thus affects leukocytes via direct or indirect means: immune cells are either present in tissues during treatment, or infiltrate or exfiltrate plasma-treated areas. The immune system is crucial for human health and resolution of many types of diseases. It is therefore vital to study the response of leukocytes after plasma treatmentin vitroandin vivo. This review gathers together the major themes in the plasma treatment of innate and adaptive immune cells, and puts these into the context of wound healing and oncology, the two major topics in plasma medicine.

scholarly journals Crosstalk between Red Blood Cells and the Immune System and Its Impact on Atherosclerosis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Brigitta Buttari ◽  
Elisabetta Profumo ◽  
Rachele Riganò
Keyword(s):  
Oxidative Stress ◽  
Immune System ◽  
Red Blood Cells ◽  
Immune Cells ◽  
Blood Cells ◽  
Atherosclerotic Disease ◽  
Intraplaque Hemorrhage ◽  
Immune System Activation ◽  
Adaptive Immune Cells ◽  
The Impact

Atherosclerosis is a chronic multifactorial disease of the arterial wall characterized by inflammation, oxidative stress, and immune system activation. Evidence exists on a pathogenic role of oxidized red blood cells (RBCs) accumulated in the lesion after intraplaque hemorrhage. This review reports current knowledge on the impact of oxidative stress in RBC modifications with the surface appearance of senescent signals characterized by reduced expression of CD47 and glycophorin A and higher externalization of phosphatidylserine. The review summarizes findings indicating that oxidized, senescent, or stored RBCs, due to surface antigen modification and release of prooxidant and proinflammatory molecules, exert an impaired modulatory activity on innate and adaptive immune cells and how this activity contributes to atherosclerotic disease. In particular RBCs from patients with atherosclerosis, unlike those from healthy subjects, fail to control lipopolysaccharide-induced DC maturation and T lymphocyte apoptosis. Stored RBCs, accompanied by shedding of extracellular vesicles, stimulate peripheral blood mononuclear cells to release proinflammatory cytokines, augment mitogen-driven T cell proliferation, and polarize macrophages toward the proinflammatory M1 activation pathway. Collectively, literature data suggest that the crosstalk between RBCs with immune cells represents a novel mechanism by which oxidative stress can contribute to atherosclerotic disease progression and may be exploited for therapeutic interventions.

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