IMMUNE STIMULATION BY AN ANTISENSE OLIGOMER COMPLEMENTARY TO THE REV GENE OF HIV-1

Mice developed massive splenomegaly and polyclonal hypergammaglobuline mia within 2 days after intravenous injection of a phosphorothioate ol igomer that is antisense to a portion of the rev region of the HIV-1 g enome. Histologic examination of spleens from injected animals showed marked expansion of a uniform-appearing population of small lymphocyte s and many mitoses. Spleen mononuclear cells (SMNCs) from injected ani mals showed approximately a 10-fold-increased uptake of [H-3]thymidine and production of IgM and IgG. Flow cytometry analysis indicated that the responding cells were predominantly B-lymphocytes. The anti-rev o ligomer also was mitogenic in vitro and stimulated immunoglobulin prod uction by normal mouse SMNCs and human peripheral blood mononuclear ce lls. Similar immunologic effects were observed with an anti-rev 21-mer phosphorothioate, truncated at the 3' end, but not with a 20-mer huma n p53 antisense phosphorothioate or a 28-mer anti-rev phosphodiester. These observations are consistent with the possibility that DNA sequen ces homologous to the rev gene participate in the regulation of mammal ian lymphocyte activation, proliferation and maturation.