Studies on the sensitization of animals with simple chemical compounds. XII. The influence of excision of allergenic depots on onset of delayed hypersensitivity and tolerance.

In light of knowledge of the rate and route of dispersal of allergenic chemicals from ear sites (0.25 microg of picryl chloride, or 2:4 dinitrochlorobenzene in 0.25 microg and 5.0 microg amounts), dispersal was interrupted at selected times by ear excision. The animals exposed in this manner to different, tiny amounts of allergen were tested for development of contact type hypersensitivity. Both of these allergenic chemicals left the local ear site in about three phases of successively lengthening "half-lives." In the first phase, the escape rate was high. The principal pathway of escape was not via the lymphatics but via the blood vessels. Ear excisions made at 24 hr after injection of 0.25 microg of picryl chloride (PCl) or at 12 hr after injection of 5.0 microg of dinitrochlorobenzene (DNCB) essentially blocked onset of delayed type hypersensitivity, hence the first fraction to escape (80% of PCl, 98% of DNCB) was not used for sensitization. This large fraction serves rather to set up a state of specific tolerance, for these individuals showed extensive deficits in their ability to respond to a later sensitizing course. Also the ability to form hapten-specific antibody appeared nearly completely suppressed. Injections of allergen into the blood stream or directly in auricular nodes, in an amount approximating that which escaped early from the ear, also led to the same degrees of unresponsiveness-sometimes full, sometimes partial tolerance. The same types of specific tolerance were secured also by injecting subsensitizing doses into the ear, without excision, or into the flank and by contact tests applied to the flank. The allergen remaining in the ear after the early outflow, particularly between 12-24 hr and 3-4 days, appeared to constitute the sensitizing depot. The longer this depot was available to the animals the greater the immunological "information" for sensitization was picked up until the depot had served its full function around the 4th day. "Peripheral sensitization" was clearly demonstrable. The eventual degree of sensitivity attained by the animals was a resultant of two immunologic processes which occurred independently-tolerogenic effects of escaped chemical on the one hand and on the other the sensitizing effect of the local sensitizing depot of allergen bound in the ear tissue.