Splicing Pattern of mRNA in Thymus Epithelial Cells Limits the Transcriptome Available for Negative Selection of Autoreactive T Cells

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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Autoimmunity-Associated LYP-W620 Does Not Impair Thymic Negative Selection of Autoreactive T Cells

PLoS ONE ◽

10.1371/journal.pone.0086677 ◽

2014 ◽

Vol 9 (2) ◽

pp. e86677 ◽

Cited By ~ 18

Author(s):

Dennis J. Wu ◽

Wenbo Zhou ◽

Sarah Enouz ◽

Valeria Orrú ◽

Stephanie M. Stanford ◽

...

Keyword(s):

T Cells ◽

Negative Selection ◽

Autoreactive T Cells ◽

Selection Of

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

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1072067.525050 ◽

2007 ◽

Author(s):

Bruno Kyewski

Keyword(s):

T Cells ◽

Epithelial Cells ◽

Regulatory T Cells ◽

Thymic Epithelial Cells ◽

Medullary Thymic Epithelial Cells ◽

Self Antigen ◽

Selection Of

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In Pursuit of Adult Progenitors of Thymic Epithelial Cells

Frontiers in Immunology ◽

10.3389/fimmu.2021.621824 ◽

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.

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