Abstract
Thymus is an organ well studied of cell differentiation and tumorigenesis. Thymus provides a specialized environment that supports proliferation and maturation. However, formation of the thymus and thymocyte development depend on bidirectional signals between the developing T cells and the thymic stroma. Many signaling molecules that are produced by stroma cells, including proteins in Notch signaling, control thymocyte proliferation and differentiation and also elimination of unfavorable cells generated during the processes. Accordingly, the loss of Notch1 signaling results in developmental block whereas the overexpression leads to thymic lymphomas by rendering cells independent of the supply of Notch ligands. Failure to eliminate unregulated proliferating cells is a cause of cancer. Fractionated whole-body γ-irradiation to mice induces thymic lymphomas after the persistence of thymic atrophy, which probably contains prelymphoma cells. However, it is unclear how irradiation contributes to lymphoma development and of hallmarks of the prelymphomas. We have characterized thymocytes in radiation-damaged thymus and changes in signaling. Most those thymuses comprised clonally expanding thymocytes that exhibited hindrance in the cell-cycle progression and high levels of reactive oxygen species. Also, Nrp-1 expression on the cell surface decreased, which may change thymocyte-stromal cell interactions within thymus. We propose that the hallmark of the prelymphoma cells is the coexistence of activation and inhibition of cell cycle accompanying with evasion from stromal inhibitory signals.
