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Immunology
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Teaching and Learning Immunology. Information you never would have searched for!
Curated by
Gilbert C FAURE
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The preimmune repertoire consists of mature T lymphocytes that have not yet been stimulated in the periphery. Memory phenotype (MP) cells have been reported as part of the preimmune repertoire (i.e., T cells bearing memory markers despite lack of engagement with cognate Ag); however, little is known about their trafficking and function. In this study, we hypothesized that MP cells, naive to TCR stimulation, constitute a transient population that traffics to tissues during development. Using mutant and transgenic animals with a monospecific TCR, we discovered increased numbers of MP CD8+ T cells circulating in nonimmunized Cxcr3−/− and Cxcl10 −/− mice compared with wild-type animals. Phenotypic differences included decreased numbers of preimmune MP Ag-specific T cells in the skin and thymus and a distinct pattern of activation upon TCR engagement. Our results show for the first time, to our knowledge, an important role for CXCR3 and CXCL10 in the tissue distribution of preimmune MP cells. 
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bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
Gilbert C FAURE's insight:
Ageing is characterised by cellular senescence, leading to imbalanced tissue maintenance, cell death and compromised organ function. This is first observed in the thymus, the primary lymphoid organ that generates and selects T cells. However, the molecular and cellular mechanisms underpinning these ageing processes remain unclear. Here, we show that mouse ageing leads to less efficient T cell selection, decreased self-antigen representation and increased T cell receptor repertoire diversity. Using a combination of single-cell RNA-seq and lineage-tracing, we find that progenitor cells are the principal targets of ageing, whereas the function of mature thymic epithelial cells is compromised only modestly. Specifically, an early-life precursor cell population, retained in the mouse cortex postnatally, is virtually extinguished at puberty. Concomitantly, a medullary precursor cell quiesces, thereby impairing maintenance of the medullary epithelium. Thus, ageing disrupts thymic progenitor differentiation and impairs the core immunological functions of the thymus.
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Eur J Immunol. 2015 Jun 24. doi: 10.1002/eji.201545829. [Epub ahead of print]
Gilbert C FAURE's insight:
Abstract
The thymus is an anatomically compartmentalized primary lymphoid organ that fosters the production of self-tolerant T cells. The thymic cortex provides a specialized microenvironment in which cortical thymic epithelial cells (cTECs) support the positive selection and further differentiation of self-MHC-restricted thymocytes. Following their migration into the medulla, positively selected thymocytes are further screened for self-reactivity, which involves both negative selection and Foxp3+ regulatory T-cell generation via interactions with medullary thymic epithelial cells (mTECs). Given the importance of both cortical and medullary microenvironments for T-cell development, studies that address the developmental origins of cTECs and mTECs are important in understanding the processes that shape the developing T-cell receptor repertoire, and reduce the frequency of self-reactive T cells that initiate autoimmune disease. In this issue of the European Journal of Immunology, Onder et al. [Eur. J. Immunol. 2015.45: XXXX-XXXX] identify a subset of podoplanin+ mTECs in mice that reside at the cortico-medullary junction, and show that their development is important to establish self-tolerance, and require the presence of self-reactive T cells. Collectively, their findings highlight the cortico-medullary junction as a potential repository for precursors of the mTEC lineage, and provide a better understanding of thymus medulla formation. This article is protected by copyright. All rights reserved.
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