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.
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004140:Dinitrophenols / Q000276:immunology; D006241:Haptens / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects*; D007074:Immunoglobulin G / Q000276:immunology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009712:Nucleotides, Cyclic / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013806:Theophylline / Q000494:pharmacology
D004140:Dinitrophenols; D006241:Haptens; D007074:Immunoglobulin G; D009712:Nucleotides, Cyclic; D010726:Phosphodiesterase Inhibitors; D000628:Aminophylline; D003995:Dibutyryl Cyclic GMP; D003994:Bucladesine; D013806:Theophylline