Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 203, Issue 13, Pages 2929-2937Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20062206
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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 V alpha 14 NKT cells, but not conventional CD4 T cells, selectively express high levels of interleukin (IL)-21, which preferentially induces apoptosis in B epsilon 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 B epsilon 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.
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