Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells

2007 ◽  
Vol 8 (4) ◽  
pp. 351-358 ◽  
Author(s):  
Katharina Aschenbrenner ◽  
Louise M D'Cruz ◽  
Elisabeth H Vollmann ◽  
Maria Hinterberger ◽  
Jan Emmerich ◽  
...  
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Regulatory T Cells ◽  
Thymic Epithelial Cells ◽  
Medullary Thymic Epithelial Cells ◽  
Self Antigen ◽  
Selection Of

scholarly journals The Role of Proteasomes in the Thymus

2021 ◽  
Vol 12 ◽  
Author(s):  
Melina Frantzeskakis ◽  
Yousuke Takahama ◽  
Izumi Ohigashi
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
T Cell Development ◽  
Thymic Epithelial Cells ◽  
Ubiquitinated Proteins ◽  
Self Tolerance ◽  
Essential Components ◽  
Medullary Thymic Epithelial Cells ◽  
Selection Of

The thymus provides a microenvironment that supports the generation and selection of T cells. Cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs) are essential components of the thymic microenvironment and present MHC-associated self-antigens to developing thymocytes for the generation of immunocompetent and self-tolerant T cells. Proteasomes are multicomponent protease complexes that degrade ubiquitinated proteins and produce peptides that are destined to be associated with MHC class I molecules. cTECs specifically express thymoproteasomes that are essential for optimal positive selection of CD8+ T cells, whereas mTECs, which contribute to the establishment of self-tolerance in T cells, express immunoproteasomes. Immunoproteasomes are also detectable in dendritic cells and developing thymocytes, additionally contributing to T cell development in the thymus. In this review, we summarize the functions of proteasomes expressed in the thymus, focusing on recent findings pertaining to the functions of the thymoproteasomes and the immunoproteasomes.

scholarly journals In Pursuit of Adult Progenitors of Thymic Epithelial Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Tatsuya Ishikawa ◽  
Nobuko Akiyama ◽  
Taishin Akiyama
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Adaptive Immune System ◽  
Thymic Epithelial Cells ◽  
Adaptive Immune ◽  
Peripheral T Cells ◽  
Robust Adaptive ◽  
Adult Thymus ◽  
Shed Light ◽  
Selection Of

Peripheral T cells capable of discriminating between self and non-self antigens are major components of a robust adaptive immune system. The development of self-tolerant T cells is orchestrated by thymic epithelial cells (TECs), which are localized in the thymic cortex (cortical TECs, cTECs) and medulla (medullary TECs, mTECs). cTECs and mTECs are essential for differentiation, proliferation, and positive and negative selection of thymocytes. Recent advances in single-cell RNA-sequencing technology have revealed a previously unknown degree of TEC heterogeneity, but we still lack a clear picture of the identity of TEC progenitors in the adult thymus. In this review, we describe both earlier and recent findings that shed light on features of these elusive adult progenitors in the context of tissue homeostasis, as well as recovery from stress-induced thymic atrophy.

scholarly journals CD1d-expressing Dendritic Cells but Not Thymic Epithelial Cells Can Mediate Negative Selection of NKT Cells

2003 ◽  
Vol 197 (7) ◽  
pp. 907-918 ◽  
Author(s):  
Taehoon Chun ◽  
Michael J. Page ◽  
Laurent Gapin ◽  
Jennifer L. Matsuda ◽  
Honglin Xu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Epithelial Cells ◽  
Negative Selection ◽  
Nkt Cells ◽  
Thymic Epithelial Cells ◽  
High Avidity ◽  
Fetal Thymic Organ Culture ◽  
Self Antigen ◽  
Dose Dependent ◽  
Selection Of

Natural killer T (NKT) cells are a unique immunoregulatory T cell population that is positively selected by CD1d-expressing thymocytes. Previous studies have shown that NKT cells exhibit autoreactivity, which raises the question of whether they are subject to negative selection. Here, we report that the addition of agonist glycolipid α-galactosylceramide (α-GalCer) to a fetal thymic organ culture (FTOC) induces a dose-dependent disappearance of NKT cells, suggesting that NKT cells are susceptible to negative selection. Overexpression of CD1d in transgenic (Tg) mice results in reduced numbers of NKT cells, and the residual NKT cells in CD1d-Tg mice exhibit both an altered Vβ usage and a reduced sensitivity to antigen. Furthermore, bone marrow (BM) chimeras between Tg and WT mice reveal that CD1d-expressing BM-derived dendritic cells, but not thymic epithelial cells, mediate the efficient negative selection of NKT cells. Thus, our data suggest that NKT cells developmentally undergo negative selection when engaged by high-avidity antigen or abundant self-antigen.

scholarly journals Evolutionary conserved gene co-expression drives generation of self-antigen diversity in medullary thymic epithelial cells

2016 ◽  
Vol 67 ◽  
pp. 65-75 ◽  
Author(s):  
Kristin Rattay ◽  
Hannah Verena Meyer ◽  
Carl Herrmann ◽  
Benedikt Brors ◽  
Bruno Kyewski
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Medullary Thymic Epithelial Cells ◽  
Conserved Gene ◽  
Self Antigen

scholarly journals Self-mediated positive selection of T cells sets an obstacle to the recognition of nonself

2021 ◽  
Vol 118 (37) ◽  
pp. e2100542118
Author(s):  
Balázs Koncz ◽  
Gergő M. Balogh ◽  
Benjamin T. Papp ◽  
Leó Asztalos ◽  
Lajos Kemény ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epithelial Cells ◽  
Positive Selection ◽  
Thymic Epithelial Cells ◽  
Immune Recognition ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Adaptive Immune ◽  
Selection Of

Adaptive immune recognition is mediated by the binding of peptide–human leukocyte antigen complexes by T cells. Positive selection of T cells in the thymus is a fundamental step in the generation of a responding T cell repertoire: only those T cells survive that recognize human peptides presented on the surface of cortical thymic epithelial cells. We propose that while this step is essential for optimal immune function, the process results in a defective T cell repertoire because it is mediated by self-peptides. To test our hypothesis, we focused on amino acid motifs of peptides in contact with T cell receptors. We found that motifs rarely or not found in the human proteome are unlikely to be recognized by the immune system just like the ones that are not expressed in cortical thymic epithelial cells or not presented on their surface. Peptides carrying such motifs were especially dissimilar to human proteins. Importantly, we present our main findings on two independent T cell activation datasets and directly demonstrate the absence of naïve T cells in the repertoire of healthy individuals. We also show that T cell cross-reactivity is unable to compensate for the absence of positively selected T cells. Additionally, we show that the proposed mechanism could influence the risk for different infectious diseases. In sum, our results suggest a side effect of T cell positive selection, which could explain the nonresponsiveness to many nonself peptides and could improve the understanding of adaptive immune recognition.

scholarly journals Induction of regulatory T cells from mature T cells by allogeneic thymic epithelial cells in vitro

2006 ◽  
Vol 19 (5) ◽  
pp. 404-414 ◽  
Author(s):  
Yimin Sun ◽  
Bao-Sheng Ge ◽  
Michiyuki Kasai ◽  
Clara Diffendaffer ◽  
Nancy Parks ◽  
...  
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Regulatory T Cells ◽  
Thymic Epithelial Cells

Promoter IV of the class II transactivator gene is essential for positive selection of CD4+ T cells

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3550-3559 ◽  
Author(s):  
Jean-Marc Waldburger ◽  
Simona Rossi ◽  
Georg A. Hollander ◽  
Hans-Reimer Rodewald ◽  
Walter Reith ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Epithelial Cells ◽  
Positive Selection ◽  
Negative Selection ◽  
Cd4 T Cell ◽  
Thymic Epithelial Cells ◽  
Mhcii Expression ◽  
Selection Of

Major histocompatibility complex class II (MHCII) expression is regulated by the transcriptional coactivator CIITA. Positive selection of CD4+ T cells is abrogated in mice lacking one of the promoters (pIV) of the Mhc2ta gene. This is entirely due to the absence of MHCII expression in thymic epithelia, as demonstrated by bone marrow transfer experiments between wild-type and pIV−/− mice. Medullary thymic epithelial cells (mTECs) are also MHCII− in pIV−/− mice. Bone marrow–derived, professional antigen-presenting cells (APCs) retain normal MHCII expression in pIV−/− mice, including those believed to mediate negative selection in the thymic medulla. Endogenous retroviruses thus retain their ability to sustain negative selection of the residual CD4+ thymocytes in pIV−/− mice. Interestingly, the passive acquisition of MHCII molecules by thymocytes is abrogated in pIV−/−mice. This identifies thymic epithelial cells as the source of this passive transfer. In peripheral lymphoid organs, the CD4+T-cell population of pIV−/− mice is quantitatively and qualitatively comparable to that of MHCII-deficient mice. It comprises a high proportion of CD1-restricted natural killer T cells, which results in a bias of the Vβ repertoire of the residual CD4+ T-cell population. We have also addressed the identity of the signal that sustains pIV expression in cortical epithelia. We found that the Jak/STAT pathways activated by the common γ chain (CD132) or common β chain (CDw131) cytokine receptors are not required for MHCII expression in thymic cortical epithelia.

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