Inducible nonlymphoid expression of Fas ligand is responsible for superantigen-induced peripheral deletion of T cells

Fas (CD95) and Fas ligand (FasL) play major roles in staphylococcal enterotoxin B (SEB)-induced peripheral deletion of V beta 8(+) T cells. We found that peripheral deletion was defective in radiation chimeras with nonfunctional tissue FasL, regardless of the FasL status of the bone marrow-derived cells. SEE induced a dramatic upregulation of FasL expression and function in nonlymphoid cells of liver and small intestine. This effect was resistant to inhibition by cyclosporin A, which also failed to inhibit peripheral deletion. In SCID animals nonlymphoid tissues did not express Fast in response to SEB unless transplanted lymphocytes were present. Thus, some immune responses induce Fast in nonlymphoid tissues, which in turn kills activated lymphocytes, leading to peripheral T cell deletion.