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Laboratory of Experimental Immunology, Department of Pathophysiology, Faculty of Medicine, Catholic University of Leuven; and
Laboratory of Cell Growth, Differentiation, and Development, Flanders Interuniversity Institute for Biotechnology, Catholic University of Leuven, Belgium
IL-12 is a heterodimeric cytokine produced by APC that promotes the
development of CD4+ Th1 cells and their IFN-
production after TCR/CD3 triggering. We here investigated the capacity
of IL-12 to modify the expression on T cells of CD40 ligand (CD40L or
CD154), a molecule transiently expressed on activated T cells and known
to be of utmost importance for cognate interaction with B cells and for
activation of dendritic cells and macrophages. Our data demonstrate
that IL-12 up-regulates CD40L expression on anti-CD3-activated
human peripheral blood T cells. For optimal induction of CD40L, IL-12
synergizes with IL-2 as well as with other costimulatory interactions,
such as B7/CD28. The effect of IL-12 was observed at both the protein
and the mRNA level. T cells costimulated by IL-12 provided more
efficient help for IL-4-dependent B cell proliferation and for IgG
production than when activated in the absence of IL-12. This helper
activity was blocked by an mAb against CD40L, indicating that the
effect of IL-12 on B cells is mediated indirectly through CD40L. The
data thus suggest that the effects of IL-12 on cellular and humoral
immune responses are partly mediated through CD40L induction.
This article has been cited by other articles:
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