Effects of Different Surface Expression of the CD40 Co-stimulatory Molecules on Dendritic Cell Functions
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Dendritic cell is one of the professional antigen presenting cells, and it bridges innate immunity and adaptive immunity. To fully activate naïve T cells, it requires DC to provide at least two signals, the interaction between T cell receptor and the MHC class II molecule loaded with antigen processed by DC, and the co-stimulatory signals provided by the co-stimulatory molecules expressed on DC. The identification of more and more co-stimulatory molecules expressed on DC and the studies on their functions highlight the importance of co-stimulatory molecules on the regulation of DC functions. We here hypothesized that different expression levels of co-stimulatory molecules expressed on DC is pivotal of directing DC function towards immunity, tolerance and polarization of Th1/Th2 immune response. Using CD40 as the model molecule to study the effect of its expression levels on DC functions, we found that no/low expression level of CD40 on DC induced antigen-specific immunological tolerance was due to the induction of CD4+CD25+Foxp3+ regulatory T cells, while the polarization of Th2 immune response induced by DC with medium expression level of CD40 was partially due to the impaired IL-12 production by DC during CD40 crosslinking. Our findings that different levels of co-stimulatory molecules have different regulations on DC functions has the significance in DC based immunotherapy for GVHD as well as the Th1 diseases.