The discovery of immunostimulatory DNA sequence

The concept of immunostimulatory DNA sequence was born in a long series of studies on BCG-mediated tumor resistance. DNA purified from BCG inhibited the growth of various animal tumors, augmented cell activity and induced IFN from mouse spleen cells. Further, we found two remarkable facts (1) DNA from bacteria, but not animals and plants, showed the above-mentioned immunogical activity, and (2) the activity was completely dependent on particular base sequences having CpG motifs. Research interests of immunostimulatory DNA sequences were galvanized in 1995 by the report of Krieg showing murine B cell activation with bacterial DNA containing CpG motifs [9]. Within a short period of time, a huge number of papers have been published in this field, and the study has expanded rapidly and widely. Now, it includes a number of research fields, for example, host-defense mechanisms against infection, allergy, autoimmune diseases, cytokine networks, plasmid vaccination, and therapeutic application of certain diseases [5, 8, 11, 15, 16, 29]. The response of higher animals against immunostimulatory DNA must be the most primitive but important mechanism for self-nonself discrimination against foreign DNA.