The effect of cyclic nucleotides on tolerance induction by dinitrophenyl-isologous immunoglobulin G.

When tolerance to a hapten is induced by injecting the hapten conjugated to isologous immunoglobulin (Ig) G (dinitrophenyl (DNP)-IgG), the hapten remains on the surface of the antigen binding cell (ABC) for the duration of the tolerant state. Although this has been interpreted as a receptor blockade of ABC, it does not necessarily indicate that physical blocking of antigen receptors is the only mechanism of tolerance. Data are presented which suggest that cyclic nucleotides play a role in the in vitro induction of tolerance by DNP-IgG. Agents that elevate intracellular cyclic adenosine 3',5' monophosphate (cAMP) levels were added to lymphocytes during tolerance induction in vitro by DNP-IgG. Dibutyryl cAMP, theophylline, aminophylline, and isobutyl alpha-methylxanthine were able to inhibit the induction of tolerance to DNP. On the other hand, addition of dibutyryl cyclic guanosine 3',5'-monophosphate (cGMP) to lymphocytes incubated with doses of DNP-IgG that ordinarily are too low to induce tolerance facilitated tolerance induction. The possible role of these intracellular second messengers in the induction to tolerance is discussed.