Induction of tolerance by administration of hapten-immunoglobulin conjugates is associated with decreased IL-2 and IL-4 production.

Intravenous administration of trinitrophenyl-modified isologous immunoglobulin-induced nonresponsiveness to subsequent epicutaneous painting of sensitizing doses of trinitrochlorobenzene. Isologous immunoglobulin with various degrees of trinitrophenyl substitution (11.2, 14.3, 27 and 47.3) prevented sensitization. The suppression of contact hypersensitivity was dependent on the dose of tolerogen and was hapten specific. Tolerance was inducible in mice of the strains CBA (H-2k), C57BL/6 (H-2b), and DBA/2 (H-2d) but not in Balb/C (H-2d) mice, suggesting that this trait maps outside the murine major histocompatibility complex. Tolerance induced by trinitrophenyl-modified immunoglobulin was associated with decreased hapten-induced proliferation of draining lymph-node cells. Unlike in other models of tolerance in which a decreased interleukin-2 to interleukin-4 ratio can be observed, administration of tolerizing trinitrophenylated immunoglobulin was associated with deficient hapten-induced release of both interleukin-2 and interleukin-4.