EFFECT OF DIFFERENT CHEMICALLY-MODIFIED OLIGODEOXYNUCLEOTIDES ON IMMUNE STIMULATION

Based on previous studies that certain oligonucleotides can stimulate cell proliferation and immunoglobulin production, this study was carri ed out to establish the relationship between the stimulatory effect an d the chemical modification of the oligonucleotide. First, the effects of oligonucleotide and analogs on immune stimulation were studied in vitro using murine splenic lymphocytes. Our results show that cell pro liferation and immunoglobulin production (IgG and IgM) depend on the s equence and the chemical modification of the oligonucleotide. Phosphor othioate oligodeoxynucleotides displayed a greater stimulatory effect than partially modified phosphorothioate oligonucleotides. Second, we studied the effects of these chemically modified olionucleotides after injection in mice. Massive splenomegaly and stimulation of cell proli feration were observed with some phosphorothioate oligonucleotides. Th ese effect were minimized markedly by chimeric and hybrid oligonucleot ides. We also demonstrate that in vitro the effects of oligonucleotide s on murine lymphocytes were unaffected by T cell depletion, suggestin g that oligonucleotides exert their effects mainly on the B cells.