title: Involvement of the intrinsic and extrinsic cell-death pathways in the induction of apoptosis of mature lymphocytes by the Escherichia coli heat-labile enterotoxin.
abstract: Escherichia coli heat-labile enterotoxin (LT) exhibits a broad range of immunomodulatory activities, including the induction of lymphocyte-programmed cell death. In previous studies, we have demonstrated that in vivo LT promotes apoptosis of immature T and B cells through the stimulation of endogenous glucocorticoids. In the present study, we show that the extrinsic cell-death pathway as well as the apoptosis-inducing factor do not participate in the LT-induced elimination of thymocytes. In contrast to developing lymphocytes, LT promotes the death of mature lymphocytes by both glucocorticoid- and Fas death receptor/Fas ligand-dependent mechanisms. However, the dependency of these mechanisms in the LT-induced cell-death activity seems to be different among CD4(+) and CD8(+) T cells. Altogether, our study shows that the same bacterial toxin can induce apoptosis of lymphoid cells through several mechanisms depending on the status of differentiation of these cells.
authors.affiliation: Department of Molecular Biology, University of Cantabria, Santander, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Tamayo
authors.forename: Jorge
authors.initials: J
authors.lastname: Postigo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Adalberto
authors.initials: A
authors.lastname: Benito
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ramón
authors.initials: R
authors.lastname: Merino
authors.forename: Jesús
authors.initials: J
authors.lastname: Merino
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology* / Q000494:pharmacology; D029968:Escherichia coli Proteins / Q000276:immunology* / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D051017:Apoptosis Regulatory Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D053222:Fas Ligand Protein; D019014:fas Receptor; C027538:heat-labile enterotoxin, E coli