IL-21-induced Bepsilon cell apoptosis mediated by natural killer T cells suppresses IgE responses.
J Exp Med
; 203(13): 2929-37, 2006 Dec 25.
Article
in En
| MEDLINE
| ID: mdl-17178921
ABSTRACT
Epidemiological studies have suggested that the recent increase in the incidence and severity of immunoglobulin (Ig)E-mediated allergic disorders is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination; however, the underlying mechanisms remain uncertain. Here, we demonstrate that natural killer T (NKT) cells in mice and humans play a crucial role in the BCG-induced suppression of IgE responses. BCG-activated murine Valpha14 NKT cells, but not conventional CD4 T cells, selectively express high levels of interleukin (IL)-21, which preferentially induces apoptosis in Bepsilon cells. Signaling from the IL-21 receptor increases the formation of a complex between Bcl-2 and the proapoptotic molecule Bcl-2-modifying factor, resulting in Bepsilon cell apoptosis. Similarly, BCG vaccination induces IL-21 expression by human peripheral blood mononuclear cells (PBMCs) in a partially NKT cell-dependent fashion. BCG-activated PBMCs significantly reduce IgE production by human B cells. These findings provide new insight into the therapeutic effect of BCG in allergic diseases.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunoglobulin E
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B-Lymphocytes
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Killer Cells, Natural
/
Interleukins
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Apoptosis
Language:
En
Journal:
J Exp Med
Year:
2006
Document type:
Article
Affiliation country:
Japan
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA