Evidence for a selective and multi-step model of T cell differentiation: CD4+CD8low 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+8lo) in mice transgenic for a T cell receptor (TCR) restricted by major histocompatibility complex (MHC) class I molecules. The results demonstrate that the CD4+8lo 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+8lo thymocytes are found in significant numbers in this transgenic model.

Tolerance induction by clonal deletion of CD4+8+ thymocytes in vitro does not require dedicated antigen-presenting cells.

The cellular requirements of T cell tolerance induction in the thymus by clonal deletion was investigated by using an in vitro assay: thymocytes from mice expressing a transgenic TcR specific for lymphocytic choriomeningitis virus (LCMV) and H-2Db were co-cultured with various H-2b cell types as antigen-presenting cells in the presence of the antigenic LCMV peptide. The results revealed that all cell lines examined including embryonic and transformed fibroblasts, melanoma cells, cortical thymic epithelial cells, lymphomas and neuronal cells induced an antigen dose-dependent deletion of CD4+8+ thymocytes. Similarly, highly enriched accessory cell populations from thymus and spleen (macrophages, dendritic and cortical epithelial cells, i.

Lactogenic hormone and cell type-specific control of the whey acidic protein gene promoter in transfected mouse cells.

The whey acidic protein (WAP) is a major milk protein. It is abundantly expressed in mammary epithelial cells, and its gene is controlled by lactogenic hormones. The identification of regulatory cis-acting sequences of the mouse WAP gene was so far dependent on the analysis of transgenic animals.