Comparison of Several Maturation Inducing Factors in Dendritic Cell Differentiation

Dendritic cells (DCs) are professional antigen presenting cells that have an important role in the initiation of immune response. The use of maturation factors in dendritic cell differentiation provides a promising approach in immunotherapy.

In this study, we compared tumor necrosis factor-α, polyribocytidylic acid, lipopolysacharide and CpG oligonucleotides in inducing dendritic cell maturation.

We generated immature dendritic cells with GM-CSF in combination with IL-4 from peripheral blood mononuclear adherent cells and used tumor necrosis factor-α, polyribocytidylic acid, lipopolysacharide and CpG for the induction of dendritic cell maturation. CD83 maturation marker on the dendritic cells was analyzed by flowcytometry after 7 days. In addition, mixed leukocyte reaction between dendritic cells and T cells was performed by MTT proliferation assay.

Flow cytometry results demonstrated a comparable high level of CD83 expression on the mature dendritic cells generated by TNF-α, CpG, Poly I:C, and LPS treatment of the immature dendritic cells. However, a significantly poorer proliferation of lymphocytes cocultured with the Poly I:C-treated DCs was observed compared to the CpG-treated DCs in mixed leukocyte reaction (p=0.026). Conversely, a significantly stronger proliferation of lymphocytes was observed when cocultured with TNF-α-treated DCs compared to the LPS-treated DCs (p=0.025).

Our results indicated that all of studied maturation inducing factors can be used in DC maturation but TNF-α and CpG were the preferred in vitro maturation factors. It is concluded that maturation of dendritic cells by CpG motif and TNF-α can be used to regulate immune responses.