Thymic nurse cells exhibit epithelial progenitor phenotype and create unique extra-cytoplasmic membrane space for thymocyte selection.

Thymic nurse cells (TNCs) are epithelial cells in the thymic cortex that contain as many as 50 thymocytes within specialized cytoplasmic vacuoles. The function of this cell-in-cell interaction has created controversy since their discovery in 1980. Further, some skepticism exists about the idea that apoptotic thymocytes within the TNC complex result from negative selection, a process believed to occur exclusively within the medulla. In this report, we have microscopic evidence that defines a unique membranous environment wherein lipid raft aggregates around the alphabetaTCR expressed on captured thymocytes and class II MHC molecules expressed on TNCs. Further, immunohistological examination of thymic sections show TNCs located within the cortico-medullary junction to express cytokeratins five and eight (K5 and K8), and the transcription factor Trp-63, the phenotype defined elsewhere as the thymic epithelial progenitor subset. Our results suggest that the microenvironment provided by TNCs plays an important role in thymocyte selection as well as the potential for TNCs to be involved in the maintenance of thymic epithelia.

Genomic adaptation to polyphagy and insecticides in a major East Asian noctuid pest.

The tobacco cutworm, Spodoptera litura, is among the most widespread and destructive agricultural pests, feeding on over 100 crops throughout tropical and subtropical Asia. By genome sequencing, physical mapping and transcriptome analysis, we found that the gene families encoding receptors for bitter or toxic substances and detoxification enzymes, such as cytochrome P450, carboxylesterase and glutathione-S-transferase, were massively expanded in this polyphagous species, enabling its extraordinary ability to detect and detoxify many plant secondary compounds. Larval exposure to insecticidal toxins induced expression of detoxification genes, and knockdown of representative genes using short interfering RNA (siRNA) reduced larval survival, consistent with their contribution to the insect's natural pesticide tolerance. A population genetics study indicated that this species expanded throughout southeast Asia by migrating along a South India-South China-Japan axis, adapting to wide-ranging ecological conditions with diverse host plants and insecticides, surviving and adapting with the aid of its expanded detoxification systems. The findings of this study will enable the development of new pest management strategies for the control of major agricultural pests such as S. litura.

The Antigenic Determinant That Defines Thymic Nurse Cells Is Expressed by Thymic Epithelial Progenitor Cells.

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 αßTCR+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.