Most thymocytes are known to be depleted from the thymus during T cell development, with the process of thymocyte death considered to be apoptosis. In this study we examined the mechanism of thymocyte death in the thymus of 6-week-old mice by using terminal deoxynucleotidyl transferase to detect DNA fragmentation or double strand breaks (TUNEL method). The TUNEL positive thymocytes were scattered throughout the cortex. Double staining of the section with the TUNEL method and acid phosphatase (ACP) activity showed that all the TUNEL positive cells were phagocytosed by ACP positive macrophages. An ultra-structural study revealed the presence of a substantial number of extremely small, unphagocytosed thymocytes throughout the cortex. These small unphagocytosed thymocytes were apparently dead cells, as based on several morphological features: 1) The majority were much smaller than red blood cells; 2) the nuclei were also considerably small; and 3) the extent of chromatin condensation was enormous. Importantly, these unphagocytosed dead thymocytes were TUNEL negative. These results indicate that: 1) DNA fragmentation, which is detected by the TUNEL method, is not involved in the cell death process of small unphagocytosed dead thymocytes shown in the present study; and that 2) typical apoptosis, which is characterized by DNA fragmentation, is not the dominant type of cell death in the normal murine thymus. Processes of cell death other than typical apoptosis taking place in most thymocytes require further investigation.
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