REGULATION OF T-CELL PRODUCTION IN T-CELL RECEPTOR TRANSGENIC MICE

The thymus produces many more cells than it releases into the peripher y. According to generally accepted models of T cell development most o f this loss occurs in the thymic cortex, among CD4+8+ thymocytes. An i nteresting situation arises in the case of T cell receptor (TcR) trans genic mice in which all cells can potentially be positively selected, leading to a theoretical increase of about 30-fold in the survival rat e of CD4+8+ cells and in their transition to mature CD4+8- or CD4-8+ t hymocytes. This in turn should lead to a 30-fold increase in the size of the thymic medulla, in the emigration rate and in the size of the p eripheral T cell pool. Increases in medullary or peripheral pool sizes of this magnitude are not seen in TcR transgenic mice. The question w as therefore asked whether some form of homeostatic process regulated the size of the mature T cell pool and at what level it might operate. In this report we demonstrate that the increased rate of double-posit ive to single-positive transition in the TcR transgenic mice is direct ly reflected in an increased emigration rate, and that the medulla see ms to be relatively efficient regardless of the number of cells passin g through it. However, the potential increases in emigrant numbers in TcR transgenic mice are offset by the reduced size of the CD4+8+ thymo cyte pool. It would appear then that regulation of T cell production, if it occurs, probably does so through regulation of the size of the C D4+8+ thymocyte pool. Mechanisms for regulation of this kind are not y et known.