Further studies on the prevention of tolerance induction by poly A:U.

Poly A:U, a complex of synthetic polyadenylic—polyuridylic acids, prevented tolerance induction to bovine gamma—globulin (BGG) in mice when administered 0-12 hours after a tolerogenic dose (500 μg) of BGG, as shown by haemagglutinin production and immune elimination of labelled antigen after challenge with 300 μg of aggregated BGG. Administration of poly A:U 3-6 hours after tolerogen appeared to be the most effective. It was found further that two doses of poly A:U given at 3 and 6 or 3 and 12 hours, or a double dose of 600 μg given at 3 hours after tolerogen did not increase its effectiveness beyond that of a single dose of 300 μg given at 3 hours. The finding that poly A:U, which may affect thymus-derived (T) cell function, prevented tolerance induction to a T cell-dependent antigen suggests that the action of poly A:U is on the T cell. For comparison, endotoxin, thought to affect bone marrow-derived (B) cell function, was included and it interfered with tolerance induction when given 0-72 hours after soluble BGG. This interval is in marked contrast to poly A:U which is effective at 0-12 hours after tolerogen and probably reflects a difference in mechanism of the two agents.