SELECTIVE INDUCTION OF APOPTOSIS IN MATURE T-LYMPHOCYTES BY VARIANT T-CELL RECEPTOR LIGANDS

Activation anergy, and apoptosis are all possible outcomes of T cell r eceptor (TCR) engagement. The first leads to proliferation and effecto r function, whereas the others can lead to partial or complete immunol ogical tolerance. Structural variants of immunizing peptide-major hist ocompatibility complex molecule ligands that induce selective lymphoki ne secretion or anergy in mature T cells in association with altered i ntracellular signaling events have been described. Here we describe al tered ligands for mature mouse CD4(+) T helper 1 cells that lead to T cell apoptosis by the selective expression of Fas ligand (Fast) and tu mor necrosis factor (TNF) without concomitant IL-2, IL-3, or interfero n gamma production. All ligands that stimulated cell death were found to induce FasL and TNF mRNA expression and TCR aggregation (''capping' ') at the cell surface, but did not elicit a common pattern of tyrosin e phosphorylation of the TCR-associated signal transduction chains. Th us, TCR Ligands that uniquely trigger T cell apoptosis without inducin g cytokines that are normally associated with activation can be identi fied.