TY - JOUR
T1 - Interleukin-12 regulates the production of Bacille Calmette-Guerin- induced interferon-γ from human cells in a CD40-dependent manner
AU - Méndez-Samperio, P.
AU - Ayala-Verdin, H. E.
AU - Trejo-Echeverria, A.
PY - 1999
Y1 - 1999
N2 - Interferon (IFN)-γ is a cytokine which plays a critical role in the host defence against human tuberculosis infection. There is evidence that interleukin (IL)-12 can exert a potent effect in stimulating the production of IFN-γ and it is well known that a costimulatory signal provided by CD40 may enhance IL-12 production by monocytes/macrophages. However, it is unclear whether CD40-CD40L stimulation is able to regulate the production of mycobacterial-induced IFN-γ through an IL-12-dependent pathway. In this study, we investigated the capacity of the Bacille Calmette-Guerin (BCG) strain of Mycobacterium bovis to induce the production of interferon-γ through IL-12 and/or CD40 costimulation from human cells. Our data demonstrate that anti-IL-12 antibodies markedly reduced the levels of IFN-γ produced by the BCG-stimulated human cells, while exogenous recombinant (r)IL-12 up-regulated the production of IFN-γ. In addition, the stimulatory effect of IL-12 on BCG-induced IFN-γ secretion was specific, as it was significantly abolished in the presence of anti-IL-12 antibodies. We also observed that the presence of an anti-CD40L monoclonal antibody significantly inhibited the production of IL-12 and IFN-γ by human cells activated with BCG. In contrast, an isotype control antibody showed no effect on cytokine production. Furthermore, the presence of a trimeric soluble CD40L agonist (CD40T) in cultures increased the production of IL-12 and IFN-γ. Importantly, the stimulatory capacity of CD40T on BCG-induced IFN-γ secretion was blocked by a monoclonal antibody against IL-12, indicating that the effect of CD40T on T cells was mediated through IL-12. Together, these studies are the first to demonstrate that BCG-induced IFN-γ production by human cells appears to be mediated by IL-12 in a CD40-dependent manner and suggest that CD40-CD40L activation may be a critical mediator in regulating the immune response to stimulation with BCG.
AB - Interferon (IFN)-γ is a cytokine which plays a critical role in the host defence against human tuberculosis infection. There is evidence that interleukin (IL)-12 can exert a potent effect in stimulating the production of IFN-γ and it is well known that a costimulatory signal provided by CD40 may enhance IL-12 production by monocytes/macrophages. However, it is unclear whether CD40-CD40L stimulation is able to regulate the production of mycobacterial-induced IFN-γ through an IL-12-dependent pathway. In this study, we investigated the capacity of the Bacille Calmette-Guerin (BCG) strain of Mycobacterium bovis to induce the production of interferon-γ through IL-12 and/or CD40 costimulation from human cells. Our data demonstrate that anti-IL-12 antibodies markedly reduced the levels of IFN-γ produced by the BCG-stimulated human cells, while exogenous recombinant (r)IL-12 up-regulated the production of IFN-γ. In addition, the stimulatory effect of IL-12 on BCG-induced IFN-γ secretion was specific, as it was significantly abolished in the presence of anti-IL-12 antibodies. We also observed that the presence of an anti-CD40L monoclonal antibody significantly inhibited the production of IL-12 and IFN-γ by human cells activated with BCG. In contrast, an isotype control antibody showed no effect on cytokine production. Furthermore, the presence of a trimeric soluble CD40L agonist (CD40T) in cultures increased the production of IL-12 and IFN-γ. Importantly, the stimulatory capacity of CD40T on BCG-induced IFN-γ secretion was blocked by a monoclonal antibody against IL-12, indicating that the effect of CD40T on T cells was mediated through IL-12. Together, these studies are the first to demonstrate that BCG-induced IFN-γ production by human cells appears to be mediated by IL-12 in a CD40-dependent manner and suggest that CD40-CD40L activation may be a critical mediator in regulating the immune response to stimulation with BCG.
UR - http://www.scopus.com/inward/record.url?scp=0032996212&partnerID=8YFLogxK
M3 - Artículo
SN - 0300-9475
VL - 50
SP - 61
EP - 67
JO - Scandinavian Journal of Immunology
JF - Scandinavian Journal of Immunology
IS - 1
ER -