Update onAireand thymic negative selection

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Thymic T-Cell Education: Positive & Negative Selection

TOLERANCE (which is antigen-specific) must be distinguished from immune deficiency (non-specific). Its most important manifestation, the maintenance of SELFTOLERANCE, was originally explained by the Clonal Selection theory as the result of CLONAL ABORTION of self-reactive clones. However, potentially self-reactive Tand B-cells do exist in normal individuals, leading to the recognition of the im...

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Models of Aire-Dependent Gene Regulation for Thymic Negative Selection

Mutations in the autoimmune regulator (AIRE) gene lead to autoimmune polyendocrinopathy syndrome type 1 (APS1), characterized by the development of multi-organ autoimmune damage. The mechanism by which defects in AIRE result in autoimmunity has been the subject of intense scrutiny. At the cellular level, the working model explains most of the clinical and immunological characteristics of APS1, ...

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Negative selection of T cells occurs throughout thymic development.

Thymic positive and negative selections govern the development of a self-MHC-reactive, yet self-tolerant, T cell repertoire. Whether these processes occur independently or sequentially remains controversial. To investigate these issues, we have employed tetrameric peptide-MHC complexes to fluorescently label and monitor polyclonal populations of thymocytes that are specific for moth cytochrome ...

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Thymic negative selection is functional in NOD mice

Based on analyses of multiple TCR transgenic (tg) models, the emergence of pathogenic T cells in diabetes-prone NOD mice has been ascribed to a failure to censure autoreactive clones in the thymus. In contrast, using isolated and preselected thymocytes, we show that nonobese diabetic (NOD) genetic variation impairs neither clonal deletion nor downstream transcriptional programs. However, we fin...

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Impaired thymic negative selection causes autoimmune graft-versus-host disease.

Animal models with impaired thymic negative selection do not always cause autoimmune diseases despite the development of an autoreactive T-cell repertoire. We investigated the requirements for the development of systemic autoimmune disease by using bone marrow chimeras that lacked expression of major histocompatibility complex (MHC) class II on thymic antigen-presenting cells (APCs), leading to...

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ژورنال

عنوان ژورنال: Immunology

سال: 2017

ISSN: 0019-2805

DOI: 10.1111/imm.12831