Immunostimulatory CpG-oligodeoxynucleotides cause extramedullary murine hemopoiesis

Bacterial DNA and the synthetic CpG-oligodeoxynucleotides (ODNs) derived th ereof have attracted attention because they activate cells of the adaptive immune system (lymphocytes) and the innate immune system (APCs) in a sequen ce-dependent manner. Here, we addressed whether CpG-ODNs affect hemopoiesis . Challenging mice with immunostimulatory CpG-ODN sequences led to transien t splenomegaly, with a maximum increase of spleen weight at day 6, The indu ction of splenomegaly by CpG-ODNs was sequence-specific, dose-dependent, an d associated with an increase in splenic cell count, in numbers of granuloc yte-macrophage CFUs (GM-CFUs), and early erythroid progenitors (burst-formi ng units-erythroid), The transfer of spleen cells from CpG-ODN-pretreated a nimals into lethally irradiated syngeneic mice yielded an increase of splee n CFUs, Furthermore, the challenge of sublethally irradiated mice with CpG- ODNs caused radioprotective effects, in that recovery of GM-CFUs and cytoto xic T cell function was enhanced. The increase in GM-CFU and CTL function c orrelated with an enhanced resistance to Listeria infection in irradiated m ice, We conclude from these data that CpG-ODNs trigger extramedullary hemop oiesis, and that this finding could be of therapeutic relevance in myelosup pression.