Cytokine production in association with phagocytosis of apoptotic cells by immature dendritic cells

Immature dendritic cells (iDCs) can ingest apoptotic cells, which do not lead to maturation of the iDCs. In this paper we examine the phagocytosis of apoptotic cells by iDCs in the absence of stimuli for the maturation of iDCs and the subsequent cytokine production. Phagocytosis was observed by confocal microscopy, and it increased as apoptosis proceeded. The coculturing of iDCs with apoptotic cells did not induce the maturation of iDCs even after the subsequent LPS treatment, as assessed as to the expression of MHC class II, CD80, CD86, and CD40. Moreover, IL-6 and IL-12p40 among the cytokines examined were specifically up-regulated by the coculturing at the mRNA and protein levels. The coculturing decreased the expression of MHC class II on iDCs and allogenic T cell proliferation induced by iDCs. Although anti-IL-6 antibodies only partially reversed the effect of coculturing with apoptotic cells, exogenous IL-6 decreased significantly the expression of MHC class II on iDCs and allogenic T cell proliferation induced by iDCs, raising the possibility that IL-6 may be partly involved in maintaining the immature status of iDCs in an autocrine manner.