The fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice

The role of a cell death-associated gene, fas, in T lymphocyte development and responses to antigen has been analyzed by breeding a transgenic T cell receptor specific for the 81–104 peptide of pigeon cytochrome c into fas-defective MRL- Ipr/Ipr and control MRL +/ + mice. Transgene-expressing T cells mature normally in both strains and populate peripheral lymphoid tissues in normal numbers. Mature CD4 + T cells from the Ipr/Ipr mice are resistant to suppression by high doses of antigen and to apoptotic cell death. In vivo administration of peptide antigen causes deletion of thymic T cells in both MRL- Ipr/Ipr and MRL +/ + strains. By contrast, antigen-induced deletion of peripheral T cells occurs in the MRL +/ + but not in the MRL- Ipr/Ipr strain. Therefore, the fas gene plays an essential role in activation-induced cell death in mature T lymphocytes, but not in the negative selection of immature cells in the thymus.