T cell signals: tolerance to DNFB is converted to sensitization by a separate nonspecific second signal.

These experiments explored the requirements for inducing specific activation and tolerance in T cells responsible for contact sensitivity. Intravenous injection of 107 DNP-modified syngeneic lymphoid cells (DNP-LC) leads to unresponsiveness to contact sensitization with DNFB one day later. The additional injection of concanavalin A (Con A), however, reverses to a large extent the ability of DNP-LC to induce tolerance. Subsequent experiments showed that injection of the tolerogen, DNP-LC, followed either immediately or two days later by Con A, generates antigen specific sensitivity to DNFB ear challenge without additional DNFB sensitization. Neither DNP-LC nor Con A given alone induces contact sensitization to DNFB. In addition, the ability to act together with Con A to produce sensitization depends on the nature of the haptenated cell membrane. Thus, DNP-LC cooperate well with Con A in the generation of sensitivity to DNFB but DNP-modified syngeneic thymocytes (DNP-THY) and red blood cells (DNP-RBC) do not. Since the latter cell types are deficient in the expression of Ia antigens, this result implies a requirement for recognition of I region gene products for effective synergism with Con A. These results indicate that the T cell tolerogen, DNP-LC, can be converted to an immunogen by a nonspecific second stimulus. They favor the concept that two signals are required to activate T cells, whereas presentation of only one signal, namely, antigen on an appropriate MHC background, may induce T cell tolerance.