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 enterot oxin B (SEB)-induced peripheral deletion of V beta 8(+) T cells. We found t hat peripheral deletion was defective in radiation chimeras with nonfunctio nal tissue FasL, regardless of the FasL status of the bone marrow-derived c ells. SEE induced a dramatic upregulation of FasL expression and function i n nonlymphoid cells of liver and small intestine. This effect was resistant to inhibition by cyclosporin A, which also failed to inhibit peripheral de letion. In SCID animals nonlymphoid tissues did not express Fast in respons e to SEB unless transplanted lymphocytes were present. Thus, some immune re sponses induce Fast in nonlymphoid tissues, which in turn kills activated l ymphocytes, leading to peripheral T cell deletion.