Induction of cell death in T lymphocytes by invasin via β1-integrin

Ligand binding to β 1 -integrins exerts multiple effects on cells of the immune system including adhesion, spreading, haptotaxis and costimulation of T cells activated by anti-CD3. Here we show that a high-affinity ligand for β 1 -integrins, the invasin (Inv) protein of Yersinia pseudotuberculosis, can induce cell death in T lymphocytes via a rapid process. Partially purified native Inv protein and an Inv fusion protein caused apoptotic/necrotic caspase-independent cell death in T lymphocytes as determined by phosphatidylserine exposure on the cell surface, uptake of propidium iodide, labeling of DNA strand breaks and presence of DNA ladder. Inv-induced cell death was mediated via β 1 -integrins as indicated by the fact that Inv bound to the β 1 -integrin subunit (CD29), that anti-β 1 -integrin antibodies blocked Inv-induced cell death and that Inv-induced cell death was absent in two β 1 -integrin - cell lines produced by different procedures. Killing via β 1 -integrins represents a novel pathway for cell death in T lymphocytes.