Effects of Different Surface Expression of the CD40 Co-stimulatory Molecules on Dendritic Cell Functions
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.
Liang, Zhang (2009). Functional analysis of the quantitative expression of a costimulatory molecule on dendritic cells using lentiviral vector-mediated RNA interference, J Immunol Methods 344(2):87-97