EVIDENCE FOR A SELECTIVE AND MULTISTEP MODEL OF T-CELL DIFFERENTIATION - CD4(+)CD8(LOW) THYMOCYTES SELECTED BY A TRANSGENIC T-CELL RECEPTOR ON MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULES

We have characterized a prominent (15-20 %) thymocyte population expressing CD4 at a high and CD8 at a low level (CD4(+)8(lo)) in mice transgenic for a T cell receptor (TCR) restricted by major histocompatibility complex (MHC) class I molecules. The results demonstrate that the CD4(+)8(lo) population is an intermediate stage between immature CD4(+)8(+) and end-stage CD4(+)8(-) thymocytes and that the survival of these cells crucially depends on the successful interaction of the transgenic TCR with self MHC class I molecules. In addition we demonstrate that the avidity of the interaction between TCR and self MHC class I molecules determines whether CD4(+)8(lo) thymocytes are found in significant numbers in this transgenic model. Our findings support a selective and multi-step model of T cell differentiation in the thymus.