The mechanism of tolerance in contact hypersensitivity to dinitrochlorobenzene in guinea-pigs.

Guinea-pigs made tolerant to dinitrochlorobenzene (by prior intracardiac injection of dinitrobenzene sulphonate) failed to give positive skin reactions after contact sensitization, but nevertheless had peritoneal cells which reacted with the hapten in macrophage migration inhibition (MMI) tests. This reactivity was blocked in vitro by the addition of serum from tolerant animals but not by serum from hypersensitive animals. Cells from hypersensitive guinea-pigs were anomalous, in that their reaction with hapten in MMI was not blocked by tolerant serum. Hypersensitive serum, though not active by itself in MMI, was able to prevent blocking by tolerant serum when the two sera were mixed. This was interpreted as an `unblocking' phenomenon and suggested that hypersensitive cells were insusceptible to blocking because they themselves produced an unblocking substance (antibody?), although preliminary efforts to demonstrate this directly were not successful. Hypersensitive serum had an analogous activity in vivo, since when passively transferred to otherwise tolerant animals it enabled them to produce typical skin reactions; that is, it broke tolerance. Tolerance or non-reactivity in vivo in the situation investigated thus appears to be an enhancement-like process, characterized by the presence of reactive lymphoid cells and a blocking factor (antigen–antibody complex?) detectable in the serum of the tolerant animals.