RAPID DEATH AND REGENERATION OF NKT CELLS IN ANTI-CD3-EPSILON-TREATEDOR IL-12-TREATED MICE - A MAJOR ROLE FOR BONE-MARROW IN NKT CELL HOMEOSTASIS

Natural killer T (NKT) cells express a T cell receptor (TCR) and marke rs common to NK cells, including NK1.1. In vivo, NKT cells are trigger ed by anti-CD3 epsilon MAb to rapidly produce large amounts of IL-4 an d by IL-12 to reject tumors. We show here that anti-CD3 epsilon MAb tr eatment rapidly depletes the liver (and partially the spleen) of NKT c ells and that homeostasis is achieved 1 to 2 days later via NKT cell p roliferation that occurs mainly in bone marrow. Similar results were o btained in mice treated with IL-12. Collectively, our data demonstrate that peripheral NKT cells are highly sensitive to activation-induced cell death and that bone marrow plays a major role in restoring NKT ce ll homeostasis.