ONTOGENY OF T-CELL MATURATION IN LEC MUTANT RATS WHICH BEAR A CONGENITAL ARREST OF MATURATION FROM CD4+CD8+ TO CD4+CD8- THYMOCYTES

LEC rats bear a congenital deficiency in CD4+CD8- thymocytes and peripheral CD4+ T cells, and consequently a deficiency in T(h) cell functions. Ontogeny of T cell maturation in normal and LEC mutant rats was, therefore, investigated. Prenatal development of thymocytes in normal rat strains, with respect to the expression of CD4/CD8 and TcR antigens, was similar to that of mice except that its kinetics was delayed by approximately 24 h. The kinetics of T cell maturation in LEC rats was comparable with that of normal rats up to day 19 of gestation, at which stage double-negative thymocytes (CD4-CD8-) developed into double positives (CD4+CD8+) through immature CD4-CD8+. subset. At day 19 of gestation in LEC as well as normal rats, double positives occupied approximately 80% of the total thymocytes, half of which were TcR-dull positive, indicating that TcR was normally rearranged and then expressed in LEC rat thymocytes. These data indicate that double negatives normally mature into at least double positives in LEC rats. Both single positives appeared after day 19 of gestation in normal rats, while in LEC rats CD4+CD8- cells did not appear, suggesting that the deficiency in CD4+CD8- cells is due to a congenital arrest of maturation from CD4+CD8+ to CD4+CD8- cells, but not due to a postnatal deletion.