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J. Exp. Med.,
Volume 187, Number 3, February 2, 1998 349-355
By
From the * Molecular Development of the Immune System Section and Activation, anergy, and apoptosis are all possible outcomes of T cell receptor (TCR) engagement. The first leads to proliferation and effector function, whereas the others can lead to partial or complete immunological tolerance. Structural variants of immunizing peptide-major
histocompatibility complex molecule ligands that induce selective lymphokine secretion or anergy in mature T cells in association with altered intracellular signaling events have been described. Here we describe altered ligands for mature mouse CD4+ T helper 1 cells that lead to
T cell apoptosis by the selective expression of Fas ligand (FasL) and tumor necrosis factor
(TNF) without concomitant IL-2, IL-3, or interferon Lymphocyte Biology Section,
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, Maryland 20892
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 tyrosine phosphorylation of the TCR-associated signal transduction chains. Thus, TCR ligands that uniquely trigger T
cell apoptosis without inducing cytokines that are normally associated with activation can be
identified.
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