The differentiation of T lymphocytes. V. Evidence for intrathymic death of most thymocytes.

The DNA of CBA mouse thymocytes was simultaneously labelled with the efficiently reutilized precursor [3H]TdR and the poorly reutilized precursor [125I]UdR, and the subsequent rate of loss of the two thymidine analogues was used to compute the extent of local thymidine reutilization. This should provide a minimum estimate of thymocyte death within the thymus. In agreement with published data, reutilization of thymidine in the "steady state' adult mouse thymus was about 61%. Adrenalectomy was used to show that this turnover was not due to steroid mediated stress effects; nor could it be attributed to direct effects of [125I]UdR itself. Most of the initial uptake and the subsequent turnover was within the major "high theta' thymus subpopulation. A similar study with the growing thymus of 7-day-old mice, when the demand for T cells in the periphery should be high, also revealed a high level (63%) of thymidine reutilization. The results support the view that a minimum of 60% of newly formed thymocytes die within the tyhmus, and that this is a constant and normal aspect of thymus function. This would be compatible with some form of negative selection for the appropriate developing T cells.