CHANGES IN HEAT-SHOCK PROTEIN-SYNTHESIS AND HEAT SENSITIVITY DURING MOUSE THYMOCYTE DEVELOPMENT

Heat shock protein synthesis was examined in mouse thymocytes at three stages of development: early embryonic thymocytes, which are CD4-CD8- , adult thymocytes, which are primarily CD4+CD8+, and mature spleen T cells, which are CD4+CD8- or CD4-CD8+. After either a 41-degrees-C or 42-degrees-C heat shock, the synthesis of the major heat-inducible pro tein (hsp68) was elevated during the first hour of recovery but then d ecreased abruptly in thymocytes from adult mice. In contrast, the synt hesis of hsp68 continued for up to 4 h after heating embryonic mouse t hymocytes or mature spleen T cells. The more rapid termination of the heat shock response in the adult thymocytes was not the result of eith er less heat damage or more rapid repair since the recovery of general protein synthesis was more severely delayed in these cells. As well, the double positive CD4+CD8+ cells were more sensitive to hyperthermia than either the double negative CD4-CD8- or single positive CD4+CD8- or CD4-CD8+ cells. Exposure of fetal thymus organ cultures to elevated temperature revealed that the double negative thymocytes were able to survive and differentiate normally following a heat shock treatment t hat was lethal for the double positive thymocytes. Exposure of thymocy tes from adult mice to elevated temperatures induced apoptotic cell de ath. This was evident by the cleavage of DNA into oligonucleosome-size d fragments. Quantitation of the extent of DNA fragmentation and the n umber of apoptotic cells by flow cytometry demonstrated that the exten t of apoptotic cell death was related to the severity of the heat stre ss. Double positive (CD4+CD8+) thymocytes are selected on the basis of their T-cell antigen receptor (TCR). Most of these cells are negative ly selected and die within the thymus by an active process of cell del etion known as apoptosis. Restricting hsp synthesis in response to str ess might be essential during developmental processes in which cell ma turation is likely to result in death rather than functional different iation.