Mechanism underlying superantigen-induced clonal deletion of mature T lymphocytes.
We observed that peripheral T cells activated in vivo or in vitro by superantigens are susceptible to cell death when their antigen receptor is cross-linked with the appropriate anti-alpha beta TCR mAb. TCR ligation by mAbs specifically drove the T cell clonal deletion in both CD4+ and CD8+ cell subsets. An IL-2/IL-2R interaction seems to be a critical step in predisposing superantigen activated cells to death; in fact, in vivo IL-2R blockade reversed T cell deletion in superantigen plus anti-alpha beta TCR mAb treated mice. TCR ligation by mAbs also produced cell death of the relevant targets in in vitro IL-2 activated T cells. Surprisingly, no T cell deletion was demonstrable in IL-2 activated cells following staphylococcal enterotoxin B--TCR interaction, ruling out the possibility that superantigen in itself can induce cell death. Thus, while superantigen activation opens the cell death program, a subsequent TCR--antigen (self) interaction appears necessary to produce clonal deletion in mature T lymphocytes.
Biasi
G
G
Institute of Experimental Pathology, Ancona, Italy.
Panozzo
M
M
Pertile
P
P
Mezzalira
S
S
Facchinetti
A
A
D000818:Animals; D000911:Antibodies, Monoclonal; D016923:Cell Death; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007376:Interleukin-2 / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C031818:enterotoxin B, staphylococcal