APOPTOSIS AND DEVELOPMENT OF THYMOCYTES - EPITHELIAL-CELLS AS INDUCERS OF APOPTOSIS OF THE THYMOCYTES

Apoptosis, together with proliferation, is a main factor of selection of the clones of developing T-lymphocytes: the clones not supported by positive selection are subject to apoptosis and apoptosis accounts fo r discarding of potentially autoaggressive clones, i.e., for negative selection in the thymus and peripheral lymphoid tissue. Realization of apoptosis at different stages of the development of T-lymphocytes dep ends to a varying extent on Fas, Bcl-2, p53, and other regulators. The dendritic cells are the main cell type, the contact with determines a poptosis of T-lymphocytes. A possible role of the epithelial cells was shown in few models (on murine cells) and was not practically studied . We obtained a line of epithelial cells of the human thymus cells HTS C, cocultivation with which induces apoptosis of immature thymocytes a nd blood T-cells activated by mitogens. Development of apoptosis is su ppressed by inhibitors of protein and RNA synthesis, chelators Ca2+, i ons Zn2+ and factors destroying the cytoskeleton components. In this m odel, interaction of pairs of molecules CD4-HLA class II and LFA-1-ICA M-1. When in contact with the HTSC cells, the thymocytes of mice mutan t for Fas-receptor (line MRL.lpr) are subject to apoptosis, but when t his receptor is present, it affects the development of apoptosis.