[2] Both of these types of cells can be defined and reciprocally distinguished by their expression of cytokines, chemokines, costimulatory molecules, and transcription factors, which have an effect on thymocyte development.
[2] Maturation of mTEC leads to expression of high levels of MHCII, CD80, autoimmune regulator Aire and tissue restricted antigens (TRAs).
Foxn1 controls the whole process by the activation of its target genes with binding to specific DNA sequence via its forkhead box domain.
In contrast, mTEC development is dependent on the presence of Relb, NFκB signals and the TNFR superfamily but it could be performed in the absence of Foxn1.
These CD4+ and CD8+ double positive T lymphocytes already express completely recombined TCRs that are tested for recognizing self and non-self molecules by MHCI and MHCII presentation of self antigens on the cTEC.
[7] Without negative selection thymocytes are unable to respond to TCR triggering by proliferation, because of a chance of presence auto-reactive T-cell clones.
Foxp3 Treg development is supported by mTECs during negative selection, when thymocytes have TCR specificities with intermediate affinity for self antigens.
[1][7] TECs, as a component of the thymus, play a key role in thymocyte development and self-tolerance, so their dysfunction causes many autoimmune diseases, tumors of immunodeficiencies.
Autoimmune disease development is result of a breakdown of the self-tolerance by Aire-mediated TRAs' expression on mTEC or the negative regulatory system formed by CD4+CD25+Foxp3 nTreg cells.
The outcome of a single gene mutation in the autoimmune regulator Aire is systematic disease APECED (APS-1), which is manifested by mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency.