How the thymus shaped immunology and beyond

Miller, J. F. A. P.

doi:10.1111/imcb.12220

Cited by 3 publications

(1 citation statement)

References 27 publications

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“…The thymus produces multiple T cell types that play key roles in both innate and adaptive immune responses. The importance of these responses has now been shown in sister lineages of vertebrates, long after the function of the thymus was proven for jawed vertebrates in the 1960s [1,2]. Indeed, a key feature of adaptive immunity lies in its ability to generate a wide diversity of antigen receptors that target non-self.…”

Section: Thymic Medulla and The Control Of T Cell Tolerancementioning

confidence: 99%

Rethinking Thymic Tolerance: Lessons from Mice

Inglesfield

Cosway

Jenkinson

et al. 2019

Trends in Immunology

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In the thymus, distinct cortex and medulla areas emphasize the division of labor in selection events shaping the abT cell receptor repertoire. For example, MHC restriction via positive selection is a unique property of epithelial cells in the thymic cortex. Far less clear are the events controlling tolerance induction in the medulla. By acting in concert through multiple roles, including antigen production/presentation and chemokine-mediated control of migration, we propose that medullary epithelium and dendritic cells collectively enable the medulla to balance T cell production with negative selection and Foxp3 + regulatory T cell (Treg) development. We examine here the features of these medullary resident cells and their roles in T cell tolerance, and discuss how imbalance in the thymus can result in loss of T cell tolerance. Thymic Medulla and the Control of T Cell ToleranceThe thymus produces multiple T cell types that play key roles in both innate and adaptive immune responses. The importance of these responses has now been shown in sister lineages of vertebrates, long after the function of the thymus was proven for jawed vertebrates in the 1960s [1,2]. Indeed, a key feature of adaptive immunity lies in its ability to generate a wide diversity of antigen receptors that target non-self. For T cells, this is achieved by T cell receptor (TCR) gene rearrangements that take place during T cell development in the thymus. Because of the random nature of gene rearrangement, the thymus imposes stringent mechanisms that shape the abTCR repertoire. Such processes are crucial because they ensure that abT cells (see Glossary) leaving the thymus are not only biased towards the recognition of self-MHC proteins but also tolerant to self-antigens. To achieve this the thymus creates a division of labor: the cortex imposes MHC restriction via positive selection, while the medulla imposes T cell tolerance via a combination of negative selection and Foxp3 + Treg development.The generation of abT cells in the thymus involves immature thymocytes being subjected to sequential checkpoints as they undergo intrathymic migration. To ensure that the thymus produces abT cells capable of antigen recognition in peripheral tissues, the cortex supports positive selection of immature CD4 + CD8 + double-positive (DP) thymocytes that recognize selfpeptide/MHC complexes produced and expressed by cortical thymic epithelial cells (cTECs). This process rescues DP thymocytes from cell death and triggers further differentiation, including expression of the chemokine receptor CCR7 that guides newly selected thymocytes into the medulla [3,4].Because positive selection results in the survival of thymocytes that recognize self-peptide/ MHC, additional selection mechanisms ensure that T cell development produces functional thymocytes that are tolerant to self-antigens. The thymic medulla provides a specialized microenvironment to support these events, and medullary thymic epithelial cells (mTECs) and dendritic cells (DCs) combine to enforce two key proces...

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Section: Thymic Medulla and The Control Of T Cell Tolerancementioning

confidence: 99%

Rethinking Thymic Tolerance: Lessons from Mice

Inglesfield

Cosway

Jenkinson

et al. 2019

Trends in Immunology

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Effects of PRRSV Infection on the Porcine Thymus

Gang

Cai

et al. 2020

Trends in Microbiology

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Sıçanların Timusunun Histoultramikroskopik İncelenmesi (Deneysel Veri)

Prykhodko¹,

Dmytruk²,

Avilova

et al. 2021

Düzce Tıp Fakültesi Dergisi

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Aim: The research paper presents the characteristic of cytoarchitectonics of the thymus of intact white mature male laboratory rats. Topicality of the study is due to the need to clarify the data on the contribution of each type of thymus cells in the formation of its structure. The aim of the research was to determine the specifics of localization and ultramicroscopic structure of thymus cells in male mature Wistar laboratory rats. Material and Methods: The study was conducted using histological and ultramicroscopic methods on 10 mature male laboratory rats, weighing 130-150 g. Semi-thin (0.5-1 μm) and ultrathin (0.05-0.2 μm) sections were made on a microtome UMTP-4 (Ukraine), which were stained with 1% methylene blue solution with the addition of 1% sodium tetraborate solution. Histological analysis and photographic recording were performed using Olympus light microscope (Japan) and DSM 510 camcorder with magnification in 1000 times. Results: With a detailed study of the semi-thin and ultrathin sections in the thymus lobules the specifics of localization and ultramicroscopic structure of thymus cells were clearly identified. The features of localization and ultramicroscopic structure of epithelial, mesenchymal, vascular and hematopoietic thymus cells were determined from the point of view of their functional loads and interactions. Conclusion: The described structural peculiarities of the components of the thymus and their relative location in different zones reflect significant organ polymorphism, which must be taken into account in order to achieve the required level of objectivity in the result evaluation of simulated biomedical experiments.

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How the thymus shaped immunology and beyond

Cited by 3 publications

References 27 publications

Rethinking Thymic Tolerance: Lessons from Mice

Rethinking Thymic Tolerance: Lessons from Mice

Effects of PRRSV Infection on the Porcine Thymus

Sıçanların Timusunun Histoultramikroskopik İncelenmesi (Deneysel Veri)

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