TY - JOUR
T1 - Bacillus Calmette Guérin triggers the IL-12/IFN-γ axis by an IRAK-4- and NEMO-dependent, non-cognate interaction between monocytes, NK, and T lymphocytes
AU - Feinberg, Jacqueline
AU - Fieschi, Claire
AU - Doffinger, Rainer
AU - Feinberg, Max
AU - Leclerc, Tony
AU - Boisson-Dupuis, Stéphanie
AU - Picard, Capucine
AU - Bustamante, Jacinta
AU - Chapgier, Ariane
AU - Filipe-Santos, Orchidée
AU - Ku, Chung Lung
AU - de Beaucoudrey, Ludovic
AU - Reichenbach, Janine
AU - Antoni, Guillemette
AU - Baldé, Ramatoulaye
AU - Alcaïs, Alexandre
AU - Casanova, Jean Laurent
PY - 2004/11
Y1 - 2004/11
N2 - The IL-12/IFN-γ axis is crucial for protective immunity to Mycobacterium in humans and mice. Our goal was to analyze the relative contribution of various human blood cell subsets and molecules to the production of, or response to IL-11 2 and IFN-γ. We designed an assay for the stimulation of whole blood by live M. bovis Bacillus Calmette-Guérin (BCG) alone, or BCG plus IL-12 or IFN-γ, measuring IFN-γ and IL-12 levels. We studied patients with a variety of specific inherited immunodeficiencies resulting in a lack of leukocytes, or T, B, and/or NK lymphocytes, or polymorphonuclear cells, or a lack of expression of key molecules such as HLA class II, CD40L, NF-κB essential modulator (NEMO), and IL-1 receptor-associated kinase-4 (IRAK-4). Patients with deficiencies in IL-12p40, IL-12 receptor β1 chain (IL-12Rβ1), IFN-γR1, IFN-γR2, and STAT-1 were used as internal controls. We showed that monocytes were probably the main producers of IL-12, and that NK and T cells produced similar amounts of IFN-γ. NEMO and IRAK-4 were found to be important for IL-12 production and subsequent IFN-γ production, while a lack of CD40L or HLA class II had no major impact on the IL-12 /IFN-γ axis. The stimulation of whole blood by live BCG thus triggers the IL-12/IFN-γ axis by an IRAK-4- and NEMO-dependent, non-cognate interaction between monocytes, NK, and T lymphocytes.
AB - The IL-12/IFN-γ axis is crucial for protective immunity to Mycobacterium in humans and mice. Our goal was to analyze the relative contribution of various human blood cell subsets and molecules to the production of, or response to IL-11 2 and IFN-γ. We designed an assay for the stimulation of whole blood by live M. bovis Bacillus Calmette-Guérin (BCG) alone, or BCG plus IL-12 or IFN-γ, measuring IFN-γ and IL-12 levels. We studied patients with a variety of specific inherited immunodeficiencies resulting in a lack of leukocytes, or T, B, and/or NK lymphocytes, or polymorphonuclear cells, or a lack of expression of key molecules such as HLA class II, CD40L, NF-κB essential modulator (NEMO), and IL-1 receptor-associated kinase-4 (IRAK-4). Patients with deficiencies in IL-12p40, IL-12 receptor β1 chain (IL-12Rβ1), IFN-γR1, IFN-γR2, and STAT-1 were used as internal controls. We showed that monocytes were probably the main producers of IL-12, and that NK and T cells produced similar amounts of IFN-γ. NEMO and IRAK-4 were found to be important for IL-12 production and subsequent IFN-γ production, while a lack of CD40L or HLA class II had no major impact on the IL-12 /IFN-γ axis. The stimulation of whole blood by live BCG thus triggers the IL-12/IFN-γ axis by an IRAK-4- and NEMO-dependent, non-cognate interaction between monocytes, NK, and T lymphocytes.
KW - Cellular activation
KW - Cytokines
KW - Human
KW - Mycobacterium
KW - Primary immunodeficiency
UR - http://www.scopus.com/inward/record.url?scp=9244245196&partnerID=8YFLogxK
U2 - 10.1002/eji.200425221
DO - 10.1002/eji.200425221
M3 - 文章
C2 - 15384045
AN - SCOPUS:9244245196
SN - 0014-2980
VL - 34
SP - 3276
EP - 3284
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 11
ER -