Anti-alpha4 integrin antibody induces apoptosis in activated murine lymph node T cells

We have developed an in vitro system in which Staphylococcal enterotoxin B (SEB) activated murine lymph node T cells undergo apoptosis following a rechallenge with SEB. Approximately 50% of the cell are induced to die following SEB rechallenge and this apoptosis is sensitive to the PKC inhibitor Ro3 1.8425 and cyclosporin A. We have also found that cells, previously activated with SEB, can be induced to undergo apoptosis with an anti-a4 mAb (9C10) in the absence of any hrther exposure to antigen. Apoptosis induced in these cells by anti-a4 mAb is inhibited by cyclosporin A and Ro3 1.8425, in a comparable way to restimulation with SEB. We suggest that VLA-4 acitvation may be an important costimulatory factor in the induction of apoptosis in activated mature T cells. This pathway may represent one of the mechanisms whereby certain integrin-cell/ECM interactions can regulate apoptosis in activated mature T cells.