Abstract
Stromal thymic epithelial cells with the multicellular structure unique to thymic nurse cells (TNCs) express the pH91 antigen on their cell surfaces. The multicellular TNC-complexes develop through an intimate association between αβTCR+CD4+CD8+ thymocytes and pH91-expressing cortical epithelial cells. TNCs participate in MHC-restriction and exhibit epithelial cell progenitor characteristics. In this report, we show that as early as E11.5 stage of thymus development, the pH91 antigen is expressed in association with K8, K5, Foxn1, and p63. The expression of these epithelial progenitor markers along with the pH91 antigen persists throughout thymic development in the murine thymus. At E13.5, pH91+ cells express relatively low levels of MHC class II. After E17.5, the first multicellular TNC complexes are recognizable along with increased cell surface expression of MHC class II. Our data suggest that epithelial cells bearing the “progenitor phenotype” develop into the multicellular TNCs.
Highlights
The bipotent population of cells that give rise to both cortical as well as medullary epithelial cells that participate in the maintenance of self-tolerance within the organism (Gill et al, 2002; Baik et al, 2013) has received much attention in recent years
We showed in tissue section that K8 and K5 positive thymic nurse cells (TNCs) reside within the cortico-medullary junction (CMJ) of the thymus (Hendrix et al, 2010)
The results show that 76% of the epithelial cell population expressed both K8 and K5 and portrayed the multicellular morphology of TNCs, whereas 24% of the K5+K8+ cells did not exhibit the distinctive multicellular TNC phenotype (Figures 1A,B)
Summary
The bipotent population of cells that give rise to both cortical (cTECs) as well as medullary epithelial (mTECs) cells that participate in the maintenance of self-tolerance within the organism (Gill et al, 2002; Baik et al, 2013) has received much attention in recent years. Since double positive epithelial cells appear before K8+K5− or K8−K5+ single positives, it has been suggested that K8+K5+ cells are progenitors of the both single positive subsets, and give rise to cells that develop into the medulla or cortex. This theory is supported by studies in which T cell development is blocked early during the differentiation process (Klug et al, 1998). Such genetic mutations produce an “immature” thymus, which produce a stromal epithelial population that is predominantly K8+K5+ cells
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