scholarly journals The Aire family expands

2019 ◽  
Vol 216 (5) ◽  
pp. 1010-1011
Author(s):  
Adrian Liston ◽  
James Dooley
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Lymph Nodes ◽  
Thymic Epithelial Cells ◽  
T Cell Tolerance ◽  
T Cell Repertoire ◽  
Cell Tolerance ◽  
Cell Repertoire

T cell tolerance depends upon Aire-expressing cells to purge the T cell repertoire of autoreactive clones. Once thought to be the exclusive domain of thymic epithelial cells, a new study by Yamano et al. (https://doi.org/10.1084/jem.20181430) in this issue of JEM identifies ILC3-like cells in the lymph nodes with similar properties.

Shaping of the autoreactive T-cell repertoire by a splice variant of self protein expressed in thymic epithelial cells

10.1038/71540 ◽  
2000 ◽  
Vol 6 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Ludger Klein ◽  
Matthias Klugmann ◽  
Klaus-Armin Nave ◽  
V K Tuohy ◽  
Bruno Kyewski
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Splice Variant ◽  
Thymic Epithelial Cells ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Autoreactive T Cell

scholarly journals Strong T cell tolerance in parent----F1 bone marrow chimeras prepared with supralethal irradiation. Evidence for clonal deletion and anergy.

1990 ◽  
Vol 171 (4) ◽  
pp. 1101-1121 ◽  
Author(s):  
E K Gao ◽  
D Lo ◽  
J Sprent
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epithelial Cells ◽  
Tolerance Induction ◽  
Thymic Epithelial Cells ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Cd4 Cells ◽  
Clonal Deletion ◽  
Host Type

T cell tolerance induction was examined in long-term H-2-heterozygous parent----F1 chimeras prepared with supralethal irradiation (1,300 rad). Although these chimeras appeared to be devoid of host-type APC, the donor T cells developing in the chimeras showed marked tolerance to host-type H-2 determinants. Tolerance to the host appeared to be virtually complete in four assay systems: (a) primary mixed lymphocyte reactions (MLR) of purified lymph node (LN) CD8+ cells (+/- IL-2); (b) primary MLR of CD4+ (CD8-) thymocytes; (c) skin graft rejection; and (d) induction of lethal graft-vs.-host disease by CD4+ cells. Similar tolerance was observed in chimeras given double irradiation. The only assay in which the chimera T cells failed to show near-total tolerance to the host was the primary MLR of post-thymic CD4+ cells. In this assay, LN CD4+ cells regularly gave a significant antihost MLR. The magnitude of this response was two- to fourfold less than the response of normal parental strain CD4+ cells and, in I-E(-)----I-E+ chimeras, was paralleled by approximately 70% deletion of V beta 11+ cells. Since marked tolerance was evident at the level of mature thymocytes, tolerance induction in the chimeras presumably occurred in the thymus itself. The failure to detect host APC in the thymus implies that tolerance reflected contact with thymic epithelial cells (and/or other non-BM-derived cells in the thymus). To account for the residual host reactivity of LN CD4+ cells and the incomplete deletion of V beta 11+ cells, it is suggested that T cell contact with thymic epithelial cells induced clonal deletion of most of the host-reactive T cells but spared a proportion of these cells (possibly low affinity cells). Since these latter cells appeared to be functionally inert in the thymus (in contrast to LN), we suggest that the thymic epithelial cells induced a temporary form of anergy in the remaining host-reactive thymocytes. This anergic state disappeared when the T cells left the thymus and reached LN.

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 GILT in Thymic Epithelial Cells Facilitates Central CD4 T Cell Tolerance to a Tissue-Restricted, Melanoma-Associated Self-Antigen

2020 ◽  
Vol 204 (11) ◽  
pp. 2877-2886
Author(s):  
Matthew P. Rausch ◽  
Lydia R. Meador ◽  
Todd C. Metzger ◽  
Handong Li ◽  
Shenfeng Qiu ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Cd4 T Cell ◽  
Thymic Epithelial Cells ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Self Antigen

scholarly journals NF‐κB‐inducing kinase contributes to normal development of cortical thymic epithelial cells: its possible role in shaping a proper T‐cell repertoire

Immunology ◽  
2020 ◽  
Vol 160 (2) ◽  
pp. 198-208
Author(s):  
Koji Eshima ◽  
Kana Misawa ◽  
Chihiro Ohashi ◽  
Haruka Noma ◽  
Kazuya Iwabuchi
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Normal Development ◽  
Thymic Epithelial Cells ◽  
T Cell Repertoire ◽  
Cell Repertoire

Autonomous role of medullary thymic epithelial cells in central CD4+ T cell tolerance

2010 ◽  
Vol 11 (6) ◽  
pp. 512-519 ◽  
Author(s):  
Maria Hinterberger ◽  
Martin Aichinger ◽  
Olivia Prazeres da Costa ◽  
David Voehringer ◽  
Reinhard Hoffmann ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Cd4 T Cell ◽  
Thymic Epithelial Cells ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Medullary Thymic Epithelial Cells

Restricted expression of transgenic HLA-DRA gene in thymic epithelial cells and its role in acquisition of T cell tolerance to self-superantigens and processed DRα-derived peptide

1993 ◽  
Vol 23 (7) ◽  
pp. 1678-1686 ◽  
Author(s):  
Yoshinori Fukui ◽  
Ken Yamamoto ◽  
Nobuhiko Yokoyama ◽  
Tomohisa Iwanaga ◽  
Chieri Kurashima ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
T Cell Tolerance ◽  
Cell Tolerance

scholarly journals Thymic epithelial cells use macroautophagy to turn their inside out for CD4 T cell tolerance

Autophagy ◽  
2013 ◽  
Vol 9 (6) ◽  
pp. 931-932 ◽  
Author(s):  
Chunyan Wu ◽  
Martin Aichinger ◽  
Jelena Nedjic ◽  
Ludger Klein
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Cd4 T Cell ◽  
Thymic Epithelial Cells ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Inside Out
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