Sensitizing potential of 14 mono (meth) acrylates in the guinea pig.

The aim of this study was to investigate differences in the sensitizing potential of 14 mono(meth)acrylates, when tested by the guinea pig maximization test (GPMT) and Freund's complete adjuvant test (FCAT) with an identical, intradermal induction concentration. A new grading classification of the sensitization potential is proposed. Mono(meth)acrylates show a wide range of sensitizing potential. Compared with other (meth)acrylates, methyl methacrylate is a moderate sensitizer. Attention was paid to concomitant sensitization of additives. In 9 of 16 FCATs, concomitant sensitization occurred to the inhibitors hydroquinone and p-methoxyphenol.

Reversal by cyclophosphamide of tolerance in contact sensitization. Tolerance induced by prior feeding with DNCB.

Tolerance to DNCB induced by feeding guinea-pigs with the same hapten has been reversed by a single treatment with cyclophosphamide. This is paralleled by a return of the ability of T cells to proliferate in the draining lymph node following sensitization. Certain quantitative differences between this system and that previously described using intravenous DNBSO3 have been revealed. These may indicate some difference between these two mechanisms of tolerance induction.

Differing mechanisms of tolerance and desensitization to dinitrochlorobenzene in guinea pigs.

In the present paper the mechanisms of tolerance and desensitization to dinitrochlorobenzene (DNCB) contact sensitivity in guinea pigs were investigated using the methods of adoptive sensitization of tolerant and normal syngeneic recipients and cyclophosphamide-treatment of tolerant animals known to selectively inactivate suppressor lymphocytes. It was shown that desensitization of presensitized animals is caused by the direct effect of the intravenously injected hapten on the effector cells in the peripheral compartment. The immediate onset of unresponsiveness and its very short duration almost exclude the possible involvement of enhancing antibodies or suppressor cells. In the case of tolerance induced by pretreatment with dinitrobenzenesulfonic acid, suppressor cell activity is enhanced, preventing normal specific immunocompetent cells from recognizing the antigen and/or proliferating in the draining lymph nodes. Whether suppressor lymphocytes are of the B or T type is not yet known.

The immunogenicity of dinitrophenyl amino acids.

Numerous dinitrophenyl amino acid preparations injected intradermally induced contact hypersensitivity to dinitrochlorobenzene, delayed type skin reactions to DNP-amino acids, and anti-DNP antibodies in guinea pigs. Some DNP-amino adds induced precipitating anti-DNP antibodies in rabbits as well. Some of the DNP-ammo acids studied were regularly immunogenic, possible immunogenic impurities having been excluded by extensive purification procedures. Others were either constantly nonimmunogenic or irregularly immunogenic, e.g., their immunogenicity varying from one preparation lot to another. By means of extensive chemical analyses and the establishment of dose-response curves, we were able to demonstrate in most cases that the immunogenicity was not due to contamination with unreacted dinitrofluorobenzene or other DNP derivatives, to photodecomposition or other degradation products, or to DNP-protein contaminants. Nevertheless, the irregular immunogenicity of several DNP-amino acid preparations can only be explained by a highly immunogenic impurity (or impurities) which we were unable to detect analytically. The regular immunogenicity of some other DNP-amino acids (e.g. di-DNP-L-histidine) appears to be based on a "transconjugation" phenomenon, the DNP group being able to split off from its amino acid carrier and to conjugate secondarily with proteins in vivo and in vitro. Accordingly, the interpretation of some recent data concerning the immunogenicity of low molecular weight hapten-amino acids may have to be reevaluated.