IL-12 increases CD80 expression and the stimulatory capacity of bone marrow-derived dendritic cells

Abstract

Dendritic cells (DC) are potent antigen-presenting cells derived from CD34 bone marrow stem cells. They undergo a series of maturational steps that allow them to stimulate primary T cell responses. Several cytokines are known to contribute to this process. In this study murine DC maturing from bone marrow progenitors under the influence of granulocyte macrophage colony stimulating factor and tumour necrosis factor-α were found to produce IL-12 as measured by ELISA and by flow cytometry to detect intracellular cytokine. Administration of additional IL-12 from day 3 to 7 of culture altered the function and phenotype of DC; enhanced stimulation of T cell proliferation by DC in allogeneic mixed leukocyte reactions was associated with an increase in the surface expression of CD80 on DC. These effects were dose dependent, and were consistently seen with IL-12 at 25 ng/ml and were less marked with IL-12 at 50 ng/ml. These results show that IL-12 is both produced by DC and can increase their stimulatory capacity. The findings suggest that there may be an autocrine effect of IL-12 on DC maturation and function.