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Frontiers in Immunology 2020T cell-mediated immune tolerance is a state of unresponsiveness of T cells towards specific self or non-self antigens. This is particularly essential during... (Review)
Review
T cell-mediated immune tolerance is a state of unresponsiveness of T cells towards specific self or non-self antigens. This is particularly essential during prenatal/neonatal period when T cells are exposed to dramatically changing environment and required to avoid rejection of maternal antigens, limit autoimmune responses, tolerate inert environmental and food antigens and antigens from non-harmful commensal microorganisms, promote maturation of mucosal barrier function, yet mount an appropriate response to pathogenic microorganisms. The cell-intrinsic and cell extrinsic mechanisms promote the generation of prenatal/neonatal T cells with distinct features to meet the complex and dynamic need of tolerance during this period. Reduced exposure or impaired tolerance in early life may have significant impact on allergic or autoimmune diseases in adult life. The uniqueness of conventional and regulatory T cells in human umbilical cord blood (UCB) may also provide certain advantages in UCB transplantation for hematological disorders.
Topics: Age Factors; Animals; Cord Blood Stem Cell Transplantation; Humans; Immune Tolerance; Infant; Infant, Newborn; Phenotype; Receptors, Antigen, T-Cell; Self Tolerance; T-Lymphocytes; Thymus Gland; Transplantation, Homologous; Umbilical Cord
PubMed: 33329542
DOI: 10.3389/fimmu.2020.576261 -
International Journal of Molecular... Jul 2017Itch is the main chief complaint in patients visiting dermatologic clinics and has the ability to deeply impair life quality. Itch results from activation of cutaneous... (Review)
Review
Itch is the main chief complaint in patients visiting dermatologic clinics and has the ability to deeply impair life quality. Itch results from activation of cutaneous nerve endings by noxious stimuli such as inflammatory mediators, neurotransmitters and neuropeptides, causing itch signal transduction from peripheral skin, through the spinal cord and thalamus, to the brain cortex. Primarily noninflammatory diseases, such as uremic pruritus, cause itch through certain pruritogens in the skin. In inflammatory skin diseases, atopic dermatitis (AD) is the prototypic disease causing intensive itch by aberrant skin inflammation and epidermal barrier disruption. Recent understanding of disease susceptibility, severity markers, and mechanisms have helped to develop targeted therapy for itch in AD, including monoclonal antibodies against IL-4, IL-13, thymic stromal lymphopoietin (TSLP), IgE and IL-31. Promising effects have been observed in some of them. In this review, we summarized targeted therapies for inflammatory itch in AD and for managing abnormal itch transductions in other common itching skin diseases.
Topics: Animals; Antibodies; Cytokines; Dermatitis, Atopic; Humans; Interleukin-13; Interleukin-4; Pruritus; Thymic Stromal Lymphopoietin
PubMed: 28698528
DOI: 10.3390/ijms18071485 -
Kardiochirurgia I Torakochirurgia... Dec 2023Mediastinal tumors encompass a diverse range of malignancies, originating within or spreading to the mediastinum. The administration of radiotherapy within the... (Review)
Review
Mediastinal tumors encompass a diverse range of malignancies, originating within or spreading to the mediastinum. The administration of radiotherapy within the anatomical confines of the mediastinum presents unique challenges owing to the close proximity of critical organs, including the heart, lungs, esophagus, and spinal cord. However, recent progress in imaging techniques, treatment modalities, and our understanding of tumor biology has significantly contributed to the development of effective and safe therapeutic strategies for mediastinal diseases. This review article aims to explore the latest innovations in radiotherapy and their practical applications in the management of mediastinal tumors, with a primary focus on lymphomas, thymomas, and thymic carcinomas. By examining these advancements, we seek to provide valuable insights into the current state of the art in radiotherapy for mediastinal malignancies, ultimately fostering improved patient outcomes and clinical decision-making.
PubMed: 38283558
DOI: 10.5114/kitp.2023.134132 -
Nature Communications Aug 2021T cells are pivotal effectors of the immune system and can be harnessed as therapeutics for regenerative medicine and cancer immunotherapy. An unmet challenge in the...
T cells are pivotal effectors of the immune system and can be harnessed as therapeutics for regenerative medicine and cancer immunotherapy. An unmet challenge in the field is the development of a clinically relevant system that is readily scalable to generate large numbers of T-lineage cells from hematopoietic stem/progenitor cells (HSPCs). Here, we report a stromal cell-free, microbead-based approach that supports the efficient in vitro development of both human progenitor T (proT) cells and T-lineage cells from CD34cells sourced from cord blood, GCSF-mobilized peripheral blood, and pluripotent stem cells (PSCs). DL4-μbeads, along with lymphopoietic cytokines, induce an ordered sequence of differentiation from CD34 cells to CD34CD7CD5 proT cells to CD3αβ T cells. Single-cell RNA sequencing of human PSC-derived proT cells reveals a transcriptional profile similar to the earliest thymocytes found in the embryonic and fetal thymus. Furthermore, the adoptive transfer of CD34CD7 proT cells into immunodeficient mice demonstrates efficient thymic engraftment and functional maturation of peripheral T cells. DL4-μbeads provide a simple and robust platform to both study human T cell development and facilitate the development of engineered T cell therapies from renewable sources.
Topics: Adaptor Proteins, Signal Transducing; Animals; Antigens, CD34; Calcium-Binding Proteins; Cell Lineage; Cell- and Tissue-Based Therapy; Cells, Cultured; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Lymphopoiesis; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Pluripotent Stem Cells; Primary Immunodeficiency Diseases; T-Lymphocytes
PubMed: 34408144
DOI: 10.1038/s41467-021-25245-8 -
Frontiers in Immunology 2023T cells have an essential role in adaptive immunity against pathogens and cancer, but failure of thymic tolerance mechanisms can instead lead to escape of T cells with... (Review)
Review
T cells have an essential role in adaptive immunity against pathogens and cancer, but failure of thymic tolerance mechanisms can instead lead to escape of T cells with the ability to attack host tissues. Multiple sclerosis (MS) occurs when structures such as myelin and neurons in the central nervous system (CNS) are the target of autoreactive immune responses, resulting in lesions in the brain and spinal cord which cause varied and episodic neurological deficits. A role for autoreactive T cell and antibody responses in MS is likely, and mounting evidence implicates Epstein-Barr virus (EBV) in disease mechanisms. In this review we discuss antigen specificity of T cells involved in development and progression of MS. We examine the current evidence that these T cells can target multiple antigens such as those from pathogens including EBV and briefly describe other mechanisms through which viruses could affect disease. Unravelling the complexity of the autoantigen T cell repertoire is essential for understanding key events in the development and progression of MS, with wider implications for development of future therapies.
Topics: Humans; Herpesvirus 4, Human; Multiple Sclerosis; Epstein-Barr Virus Infections; Brain; Central Nervous System
PubMed: 38022632
DOI: 10.3389/fimmu.2023.1304281 -
Lab Animal Jul 2023Humanized mouse models, created via transplantation of human hematopoietic tissues into immune-deficient mice, support a number of research applications, including... (Review)
Review
Humanized mouse models, created via transplantation of human hematopoietic tissues into immune-deficient mice, support a number of research applications, including transplantation immunology, virology and oncology studies. As an alternative to the bone marrow, liver, thymus humanized mouse, which uses fetal tissues for generating a chimeric human immune system, the NeoThy humanized mouse uses nonfetal tissue sources. Specifically, the NeoThy model incorporates hematopoietic stem and progenitor cells from umbilical cord blood (UCB) as well as thymus tissue that is typically discarded as medical waste during neonatal cardiac surgeries. Compared with fetal thymus tissue, the abundant quantity of neonatal thymus tissue offers the opportunity to prepare over 1,000 NeoThy mice from an individual thymus donor. Here we describe a protocol for processing of the neonatal tissues (thymus and UCB) and hematopoietic stem and progenitor cell separation, human leukocyte antigen typing and matching of allogenic thymus and UCB tissues, creation of NeoThy mice, assessment of human immune cell reconstitution and all experimental steps from planning and design to data analysis. This entire protocol takes a total of ~19 h to complete, with steps broken up into multiple sessions of 4 h or less that can be paused and completed over multiple days. The protocol can be completed, after practice, by individuals with intermediate laboratory and animal handling skills, enabling researchers to make effective use of this promising in vivo model of human immune function.
Topics: Humans; Animals; Mice; Immune System; Thymus Gland; Disease Models, Animal; Liver; Research Personnel
PubMed: 37386161
DOI: 10.1038/s41684-023-01196-z -
Hematology/oncology and Stem Cell... Jun 2021While umbilical cord blood is increasingly utilized as a stem cell source, immune complications associated with the procedure have been recognized. These complications... (Review)
Review
While umbilical cord blood is increasingly utilized as a stem cell source, immune complications associated with the procedure have been recognized. These complications result from significant immune system dysregulation and defective reconstitution following transplant causing an imbalance between T-cell subsets, aberrant B cells, and abnormal antibody production. This may occur up to 12 months after transplant coinciding with thymic regeneration in adults. The aim of our review is to describe the incidence, pathophysiology, clinical features, and prognosis of autoimmune cytopenias following umbilical cord blood transplant. Furthermore, we review the treatment strategies reported in the existing literature, describe the authors' experience with the complication, and highlight novel treatment options being studied. The knowledge of the occurrence and timing of autoimmune complications of umbilical cord blood transplantation is essential for detection and treatment of the disease. Emerging therapeutic options include interleukin-2 (IL-2), which is also being studied for the treatment of acute and chronic graft-versus-host disease. IL-2 has favorable effects on growth, differentiation, and function of regulatory T cells. Monoclonal antibody treatments, such as daratumumab, are also on the forefront and more experience with them will guide further treatment strategies.
Topics: Anemia; Animals; Antibodies, Monoclonal; Autoimmune Diseases; B-Lymphocytes; Cord Blood Stem Cell Transplantation; Humans; Interleukin-2; Neutropenia; Purpura, Thrombocytopenic, Idiopathic; T-Lymphocytes
PubMed: 32882204
DOI: 10.1016/j.hemonc.2020.07.009 -
World Journal of Clinical Cases Jan 2023Thymic lipofibroadenomas are extremely rare. In this study, we investigated the clinicopathological characteristics of thymic lipofibroadenomas.
BACKGROUND
Thymic lipofibroadenomas are extremely rare. In this study, we investigated the clinicopathological characteristics of thymic lipofibroadenomas.
CASE SUMMARY
This study included three patients with thymic lipofibroadenomas. We retrospectively analyzed the patient data to determine the clinicopathological characteristics of thymic lipofibroadenomas. The study included one man and two women [mean age, 43 (33-59) years]. All patients were non-smokers and presented with well-defined anterior mediastinal tumors. The cut surfaces of the tumors were solid, with a mixture of yellow and white areas. Microscopic evaluation of resected specimens showed scattered cord-like structures of epithelial cells embedded within abundant fibrotic and hyaline stroma admixed with variable quantities of adipose tissue. One patient showed hyperplastic thymic tissue in a part of the tumor.
CONCLUSION
Thymic lipofibroadenomas are an extremely rare type of benign thymic tumor. Surgical removal of lipofibroadenomas is usually curative.
PubMed: 36687181
DOI: 10.12998/wjcc.v11.i1.164 -
Pediatric Allergy and Immunology :... Mar 2015The fetal immune system is a critical window of development. The epithelial cell-derived cytokines, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) have...
BACKGROUND
The fetal immune system is a critical window of development. The epithelial cell-derived cytokines, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) have received attention for their role in allergic responses but not been studied during this critical window. The objectives were to assess correlations among IL-33, TSLP, and IgE in umbilical cord blood samples and identify prenatal predictors of these biomarkers.
METHODS
This study utilized data and banked cord blood collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Our analytic sample comprised the 1254 women with a singleton, term birth with a cord blood sample. Spearman correlation coefficients (SCC) and logistic regression models were used to examine associations between biomarkers and identify potential predictors of elevated biomarker levels.
RESULTS
Thymic stromal lymphopoietin and IL-33 were more strongly correlated with each other (SCC = 0.75, p < 0.0001) than with IgE (IL-33 SCC = 0.14, TSLP SCC = 0.21). Maternal allergy, heavy street traffic, and elevated birth weight were significantly associated with jointly elevated TSLP and IL-33 levels, whereas maternal age and female infant sex were inversely associated with elevated IgE.
CONCLUSIONS
In this population of Canadian women and infants, TSLP and IL-33 were detectable in cord blood, more strongly correlated with each other than with IgE, and associated with maternal characteristics indicative of inflammatory responses. This study motivates investigation into the value of cord blood IL-33 and TSLP levels as childhood allergy predictors and raises interesting questions regarding in utero coordinated regulation of these cytokines.
Topics: Adult; Birth Weight; Cytokines; Environmental Exposure; Enzyme-Linked Immunosorbent Assay; Female; Fetal Blood; Humans; Hypersensitivity; Interleukin-33; Mothers; Pregnancy; Young Adult; Thymic Stromal Lymphopoietin
PubMed: 25620084
DOI: 10.1111/pai.12340 -
Frontiers in Immunology 2018Mice engrafted with human immune cells offer powerful model systems to investigate molecular and cellular processes of tumorigenesis, as well as to test therapeutic... (Review)
Review
Mice engrafted with human immune cells offer powerful model systems to investigate molecular and cellular processes of tumorigenesis, as well as to test therapeutic approaches to treat the resulting cancer. The use of umbilical cord blood mononuclear cells as a source of human immune cells for engraftment is technically straightforward, and provides T lymphocytes and autologous antigen-presenting cells (including B cells, monocytes, and DCs) that bear cognate antigen presenting molecules. By using a human-specific oncogenic virus, such as Epstein-Barr virus, neoplastic transformation of the human B cells can be induced in a manner that models progressive stages of tumorigenesis from nascent neoplasia to the establishment of vascularized tumor masses with an immunosuppressive environment. Moreover, since tumorigenesis occurs in the presence of autologous T cells, this type of system can be used to investigate how T cells become suppressed during tumorigenesis, and how immunotherapies counteract immunosuppression. This minireview will provide a brief overview of the use of human umbilical cord blood transplanted into immunodeficient murine hosts to model antitumor responses.
Topics: Animals; Blood Transfusion; Disease Models, Animal; Fetal Blood; Graft Survival; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Immunotherapy; Lymphocyte Activation; Mice; Neoplasms; T-Lymphocytes; Thymus Gland; Xenograft Model Antitumor Assays
PubMed: 29434589
DOI: 10.3389/fimmu.2018.00054