CD4+ T cells reactivated with superantigen are both more sensitive to FasL-mediated killing and express a higher level of FasL.
Naive CD4(+) T cells proliferate strongly in response to superantigens such as staphylococcal enterotoxin B (SEB). When these cells are rested and challenged a second time, they undergo activation-induced cell death (AICD). Fas/FasL interactions have been shown to mediate AICD, even though the level of Fas expression in the 2 degrees SEB responder populations is no higher than in the 1 degrees cultures. To determine whether the dissimilarity between the 1 degrees and 2 degrees cultures could be attributed to differences in FasL cytotoxic activity or in the sensitivity of the Fas apoptosis signaling pathway, we compared these parameters during the 1 degrees and 2 degrees responses of lpr and gld CD4+ T cells (which do not undergo AICD due to a lack of Fas and an inactive FasL, respectively) so that each parameter could be evaluated independently. The results demonstrate that 2 degrees responders both express a higher level of functional FasL and are more sensitive to FasL-mediated killing. These findings account for the differences between the 1 degrees and 2 degrees responses of CD4+ T cells to superantigen. In addition, we found that the apparent level of FasL-mediated cytotoxic activity in the 2 degrees lpr CD4+ T cell population is much higher than that of wild-type cells, suggesting that deficient Fas expression leads to inordinately high levels of FasL expression or subsaturation of FasL binding sites.
Wang
J K
JK
Department of Microbiology, Boston University Medical Center, Massachusetts 02118, USA.
Zhu
B
B
Ju
S T
ST
Tschopp
J
J
Marshak-Rothstein
A
A
D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004768:Enterotoxins / Q000276:immunology / Q000494:pharmacology; D053222:Fas Ligand Protein; D007700:Kinetics; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000633:toxicity*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology / Q000494:pharmacology*; D013997:Time Factors; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics / Q000633:toxicity*
D000954:Antigens, Surface; D004768:Enterotoxins; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D018089:Superantigens; D019014:fas Receptor; C031818:enterotoxin B, staphylococcal; D012313:RNA