RAT 1ST-WAVE MATURE THYMOCYTES - CYCLING LYMPHOBLASTS THAT ARE SENSITIVE TO ACTIVATION-INDUCED CELL-DEATH BUT RESCUED BY INTERLEUKIN-2

The sequential appearance of thymocyte subsets in rat ontogeny was studied using the surface markers CD4, CD8, and the alpha/beta T cell receptor (here referred to as TcR). It was noted that the first TcR(high) thymocytes, appearing around birth, are not resting lymphocytes but cycling blast cells. These "first wave" TcR(high) cells are medullary in location and predominantly of the CD4/CD8 "single-positive" phenotype. Only about 5% express the light chain of the interleukin (IL)2 receptor, indicating that binding of IL 2 to high-affinity receptors is not driving proliferation of these blasts. Newborn TcR high blast cells were purified and analyzed in vitro. When cultured without further additions, they rapidly stopped cycling. Stimulation with cross-linked anti-TcR monoclonal antibody plus IL 2 resulted in vigorous and rapid proliferation that exhibited accelerated kinetics as compared to peripheral resting T cells. In contrast, TcR cross-linking without exogenous IL 2 induced cell death. This TcR-induced cell death involved fragmentation of DNA characteristic of apoptosis that was readily detectable within 18 h of culture. Addition of IL 2 to these short-term cultures prevented TcR-induced DNA fragmentation. Together, these results suggest that in newly formed TcR(high) thymocytes, TcR engagement results in clonal deletion if the IL 2 receptor remains unoccupied but allows clonal expansion if IL 2 is provided. This mechanism may be operative in the establishment of self-tolerance during T cell development.