ABSOLUTE DEPENDENCE OF T-CELL RECEPTOR(HI) CELL GENERATION AND RELATIVE DEPENDENCE OF T-CELL RECEPTOR(INT) CELL GENERATION ON THE THYMUS

Recent evidence indicates that conventional T cells are generated by t he mainstream of T cell differentiation in the thymus and acquire a hi gh density of T cell receptor expression (i.e. TCR(hi)). In contrast, primordial T cells (or NK1.1(+) T cells) are generated by the extrathy mic pathways or an alternative intrathymic pathway and express an inte rmediate density of TCR (i.e. TCR(int)). To obtain further evidence, i t was examined how thymus grafting influenced the distribution of T ce ll populations in athymic nude mice. When BALB/c nu/nu mice were engra fted with thymocyte-depleted BALB/c+/+ fetal thymi, two changes emerge d after grafting: nude mice generated TCR(hi) cells de novo in the per iphery as well as in the grafted thymi, and the absolute number of int erleukin-2 receptor beta chain(+)TCR(int) cells increased prominently in number in the periphery. Among thymic hormones tested, the administ ration of thymosin alpha induced a slight expansion of CD3(int) cells in nude mice. To examine a possible interaction of TCR cells with TCR( hi) cells in the periphery, B6 nu/nu mice (Ly5.2(+)) were injected wit h TCR(hi) cells purified from the spleen of B6 Ly5.1 congenic mice. In this case, TCR(int) (Ly5.2(+)) cells expanded well in all tested orga ns of nude mice. These results suggest that the generation of TCR(hi) cells is absolutely dependent on the thymus and that TCR(int) cells ex pand under the influence of the thymus (humoral) and due to interactio n with thymus-derived conventional T cells.