Unresponsiveness in hapten-specific cytotoxic lymphocytes. II. Ability of various TNP-congeners to induce unresponsiveness after repeated treatments beginning at birth

We have been investigating the induction of tolerance in cells that are involved in the generation of primary TNP-specific cell-mediated lympholysis (CML) responses in mice. In contrast with the contact hypersensitivity system, treatment of adult mice with most TNP-congeners actually primes in vitro hapten-specific CML activity. In an effort to develop a tolerance system whereby all strains of mice are rendered incapable of mounting a primary in vitro TNP-specific CML response, we tried to induce tolerance by injecting TNP-congeners immediately after birth, a time when induction of tolerance is reported to be easier, and continuing the treatments on a weekly basis to provide extended exposure to the tolerogen. The development of tolerance depends on the form of the tolerogen. Chronic treatment with hapten-modified lymphoid cells does not render mice tolerant, but actually enhances the subsequent generation of TNP-specific CML activity in vitro. In contrast, chronic treatment with TNP-modified red blood cells induces hapten-specific CML tolerance. This tolerance is strain-dependent in that BALB/c mice, but not C3H/HeN mice, were rendered unresponsive. This strain distribution is similar to that observed with TNBS-induced CML unresponsiveness in adult mice. Chronic treatment with water soluble hapten (TNBS) induces tolerance in both BALB/c and C3H/HeN mice. The unresponsiveness of these tolerant mice could be partially reversed by the addition of Con A-induced supernatants to the in vitro cultures. These latter results suggest the unresponsiveness to TNP affects at least amplifier T(H) cells and perhaps precytotoxic T cells as well. Differences in the ability of the various hapten-congeners to induce CML tolerance are discussed.