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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 -
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 -
Medicine Nov 2022Lipofibroadenoma is an extremely rare thymic tumor, and the anterior mediastinum is the most common site.
BACKGROUND
Lipofibroadenoma is an extremely rare thymic tumor, and the anterior mediastinum is the most common site.
CASE SUMMARY
A 21-year-old male was admitted with fever without obvious cause for 2 months. After admission, the patient's highest temperature was 38.3°C, accompanied by diarrhea. Physical examination showed coarse breath sounds in both lungs. Chest enhanced computed tomography (CT) showed a mass of mixed density shadow on the left side of the anterior mediastinum with a size of approximately 9.2 cm × 5 cm × 2.1 cm and a clear boundary mixed with a low fat density shadow. Mediastinal tumors were removed under general anesthesia by video-assisted thoracoscopic surgery. Macroscopically, a clear boundary was shown between the tumor and the remaining thymus. Microscopically, the tumor contained a large amount of mature adipose and fibrous tissue with scattered cord-like epithelial tissue and a small number of lymphocytes scattered in the stroma. The tumor lacked thymic bodies. The neoplastic epithelial cells were oval or polygonal and arranged in fissures, the nuclei were uniform in size and mild in shape, and mitosis was rare. Epithelial cells were positive for AE1/AE3 and CK19, lymphocytes were positive for CD3 and CD20, and fat and fibrous tissue were positive for S-100 and vimentin, respectively. The Ki67 labeling index was less than 5%. Based on histological features and immunophenotype, thymic lipofibroadenoma was diagnosed. The patient was followed up 1 year after the operation, and no recurrence or residual lesions were found on the X-ray re-examination.
CONCLUSION
Lipofibroadenoma is a benign thymic tumor, and thymectomy is regarded as the best treatment. The biological behavior of thymic lipofibroadenoma is good, and the recurrence rate is low.
Topics: Humans; Male; Young Adult; Adult; Mediastinum; Thymoma; Thymus Neoplasms; Thymectomy; Mediastinal Neoplasms
PubMed: 36401401
DOI: 10.1097/MD.0000000000031732 -
Annals of Cardiothoracic Surgery Mar 2023Robotic-assisted surgery for mediastinal disease has been shown to be beneficial in facilitating easier mediastinal dissection with its three-dimensional views and...
BACKGROUND
Robotic-assisted surgery for mediastinal disease has been shown to be beneficial in facilitating easier mediastinal dissection with its three-dimensional views and multi-articulated moving instruments. Herein, we report our experience with the biportal approach of robot-assisted anterior mediastinal mass surgery, including both lateral transthoracic and subxiphoid approaches.
METHODS
We retrospectively analyzed 21 patients who underwent biportal robotic-assisted anterior mediastinal mass resection, without considering the tumor size between May 2018 and September 2022. We reviewed the technical advantages and limitations of the biportal approach and the perioperative outcomes, including operative time, conversion to multiport or open surgery, duration of chest drainage, and postoperative complications, to define the role of robot-assisted surgery using the biportal approach.
RESULTS
We approached the thoracic cavity from the right side in five patients, from the left side in three patients, and from the subxiphoid in 13 patients. Thymomas (n=13) and thymic cysts (n=3) were the most common diagnoses. The median operative time was 165 min [interquartile range (IQR), 140-196 min]. There were no conversions to multiport or open surgery. The chest drain was removed at a median of two days (IQR, 1-3 days), and the patients were discharged at a median of four days (IQR, 3-5 days). Perioperative complications were reported in two patients (one with prolonged air leak and one with vocal cord palsy). There were no cases of readmission or delayed complication.
CONCLUSIONS
The biportal approach for robot-assisted surgery in anterior mediastinal masses is a feasible and safe alternative for treating associated pathologies. The subxiphoid approach for mediastinal surgery provides a better surgical view than the transthoracic approach. The biportal approach also enables the use of robotic staplers and energy devices and minimizes instrumental interference compared to that in the single-port approach.
PubMed: 37035644
DOI: 10.21037/acs-2022-urats-24 -
BioRxiv : the Preprint Server For... Apr 2023Within the thymus, regulation of the cellular cross-talk directing T cell development is dependent on spatial interactions within specialized niches. To create a...
Within the thymus, regulation of the cellular cross-talk directing T cell development is dependent on spatial interactions within specialized niches. To create a holistic, spatially defined map of tissue niches guiding postnatal T cell development we employed the multidimensional imaging platform CO-detection by indEXing (CODEX), as well as CITE-seq and ATAC-seq. We generated age-matched 4-5-month-old postnatal thymus datasets for male and female donors, and identify significant sex differences in both T cell and thymus biology. We demonstrate a crucial role for JAG ligands in directing thymic-like dendritic cell development, reveal important functions of a novel population of ECM fibroblasts, and characterize the medullary niches surrounding Hassall's corpuscles. Together, these data represent a unique age-matched spatial multiomic resource to investigate how sex-based differences in thymus regulation and T cell development arise, and provide an essential resource to understand the mechanisms underlying immune function and dysfunction in males and females.
PubMed: 37090676
DOI: 10.1101/2023.04.13.536804