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*
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan; and
Department of Immunology, Kumamoto University School of Medicine, Kumamoto, Japan
IL-1 is a proinflammatory cytokine that plays pleiotropic roles in
host defense mechanisms. We investigated the role of IL-1 in the
humoral immune response using gene-targeted mice. Ab production against
SRBC was significantly reduced in IL-1
/
-deficient
(IL-1-/-) mice and enhanced in IL-1R
antagonist-/- mice. The intrinsic functions of T, B, and
APCs were normal in IL-1-/- mice. However, we showed that
IL-1-/- APCs did not fully activate DO11.10 T cells,
while IL-1R antagonist -/- APCs enhanced the reaction,
indicating that IL-1 promotes T cell priming through T-APC interaction.
The function of IL-1 was CD28-CD80/CD86 independent. We found that CD40
ligand and OX40 expression on T cells was affected by the mutation, and
the reduced Ag-specific B cell response in IL-1-/- mice
was recovered by the treatment with agonistic anti-CD40 mAb both in
vitro and in vivo. These observations indicate that IL-1 enhances T
cell-dependent Ab production by augmenting CD40 ligand and OX40
expression on T cells.
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