ABSTRACT
T-cell tolerance to the minor lymphocyte-stimulating antigen Mls-1a in a T-cell receptor (TcR) V beta 8.1 transgenic line of mice is maintained by both clonal deletion and clonal anergy. Approximately 20-50% of peripheral CD4+ (but not CD8+) T cells isolated from these mice are anergic and fail to proliferate following TcR ligation. We have examined key events in T-cell signaling in peripheral T cells isolated from these mice. In this report, we show that the anergic CD4+ T cells did not mobilize calcium or express receptors for interleukin 2 (IL-2) following TcR ligation. However, the cells retained viability and functional potential because stimulation with phorbol 12-myristate 13-acetate and ionomycin bypassed the block in receptor-mediated signaling and induced IL-2 receptor expression and proliferation of the anergic cells.
Subject(s)
Immune Tolerance , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes/immunology , Animals , Antigens, Surface/genetics , CD4 Antigens/analysis , CD4 Antigens/immunology , Calcium/analysis , Chromosome Deletion , Crosses, Genetic , Gene Expression/drug effects , H-2 Antigens/genetics , Ionomycin/pharmacology , Macromolecular Substances , Mice , Mice, Inbred Strains , Mice, Transgenic , Minor Lymphocyte Stimulatory Antigens , Receptors, Antigen, T-Cell/immunology , Receptors, Interleukin-2/analysis , Receptors, Interleukin-2/genetics , Signal Transduction/drug effects , T-Lymphocyte Subsets/immunology , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
A monoclonal antibody was used to show directly positive thymic selection of the T cell repertoire in mouse strains expressing the 17a beta-chain variable domain (V beta 17a) of the T cell receptor. In the absence of the potent tolerizing class II major histocompatibility complex (MHC) molecule, I-E, peripheral expression of V beta 17a+ T cell receptors varied with the MHC haplotype of the mouse strain. In the most extreme case, H-2q mice expressed high peripheral levels of CD4+ V beta 17a+ T cells (14 to 19 percent), whereas H-2b mice expressed low levels (3 to 4 percent). Analysis of (b x q)F1 mice and chimeric mice showed that these differences were determined by positive thymic selection and implicated the thymic epithelium as the controlling cell type.