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 Vbeta8+ T cells. We found that peripheral deletion was defective in radiation chimeras with non-functional 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.
Bonfoco
E
E
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Stuart
P M
PM
Brunner
T
T
Lin
T
T
Griffith
T S
TS
Gao
Y
Y
Nakajima
H
H
Henkart
P A
PA
Ferguson
T A
TA
Green
D R
DR
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004768:Enterotoxins / Q000494:pharmacology; D053222:Fas Ligand Protein; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017403:In Situ Hybridization; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D011828:Radiation Chimera / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018089:Superantigens / Q000276:immunology / Q000494:pharmacology*
D004768:Enterotoxins; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D016572:Cyclosporine