Fas (CD95) and Fas ligand (FasL) play major roles in staphylococcal enterotoxin B (SEB)-induced peripheral deletion of Vβ8+ 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. SEB 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 FasL in response to SEB unless transplanted lymphocytes were present. Thus, some immune responses induce FasL in nonlymphoid tissues, which in turn kills activated lymphocytes, leading to peripheral T cell deletion.
Bibliographical noteFunding Information:
We thank C. Ware, R. Kluck, L. Genestier, H. Beere, and B. Wolf for critically reviewing the manuscript. This work was supported by grants from the United States National Institutes of Health (GM52735 and EY06765). E. B. was supported in part by a fellowship from the Blanceflor and Ludovisi Foundation. This is publication no. 240 of La Jolla Institute for Allergy and Immunology.
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