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The Escherichia coli heat‐labile enterotoxin induces apoptosis of immature lymphocytes in vivo via a glucocorticoid‐dependent pathway
Author(s) -
Tamayo Esther,
Merino Ramón,
GonzálezRojas Jovanna,
Marquina Regina,
Santiuste Inés,
Amado José Antonio,
Rappuoli Rino,
Del Giudice Giuseppe,
Merino Jesús
Publication year - 2005
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200526326
Subject(s) - biology , in vivo , enterotoxin , escherichia coli , apoptosis , glucocorticoid , microbiology and biotechnology , heat labile enterotoxin , immunology , biochemistry , genetics , gene
Abstract Escherichia coli heat‐labile enterotoxin (LT) exhibits a broad range of immunomodulatory activities, including the induction of lymphocyte‐programmed cell death. However, the nature of the lymphoid populations sensitive to LT‐induced apoptosis and the mechanisms used by this toxin to promote such activity are still unclear. In this study, we demonstrate that LT induces in mice a rapid increase in the levels of circulating corticosterone, resulting in a dramatic induction of cell death of immature CD4 + CD8 + , B220 + IgM – and IgM + IgD – T and B cell progenitors, respectively. Apoptosis of these cell populations is similar to that reported after experimental treatment with corticosteroids, it is inhibited by mifepristone, a glucocorticoid receptor antagonist, and does not occur in adrenalectomized animals. These results clearly indicate that endogenous glucocorticoids are the mediators of the LT‐induced cell death, which involves Bcl‐2‐dependent apoptotic pathways. The LT‐mediated programmed cell death requires systemic exposure and the enzymatic activity of LT, since a mutant devoid of any enzymatic activity have no pro‐apoptotic effect at any dose tested.