The Induction of Immunological Tolerance During the Primary Response

Abstract

By injecting adult guinea pigs intravenously with dinitrochlo-robenzene sulfonate (DNBSO₃) 2 to 24 h after applying a sensitizing epicutaneous dose of dinitrochlorobenzene (DNCB), the production of PCA-detectable anti-DNP antibodies and the induction of contact hypersensitivity to DNCB is strongly depressed for over 14 weeks. The proportion of animals acquiring this state of specific unresponsiveness as well as its stability against a second sensitizing attempt with DNCB alone are clearly dependent on the dose of DNBSO₃ injected and on the time interval elapsing between both hapten applications. However, the tolerogenic effect of DNBSO₃ is stronger when injected some weeks before sensitization. The results obtained are discussed on the basis of current concepts on the relationship between antigen and immunocompetent cells. The possibilities to interpret our findings by means of reversible blocking or affinity labelling of cellular receptors, specific annihilation of antigen-sensitive cells or immune deviation are considered.

Differing mechanisms of tolerance and desensitization to dinitrochlorobenzene in guinea pigs

“…Complete suppression of contact sensitivity was achieved by injecting the hapten intravenously. The unresponsiveness so induced was permanent when normal guinea pigs were treated with the tolerogen before the attempted sensitization (tolerance) [ 2,3], but only temporary when the hapten was applied t o presensitized animals (desensitization) [4].…”

“…The fact that only short-lasting unresponsiveness was achieved in presensitized animals was explained by the presence of a higher number of antigen-reactive cells [4]. However, in the past few years a great deal of evidence accumulated indicating that depending on whether the animals injected intravenously with the hapten were normal or sensitized, the lymphocyte activity in different cellular compartments was maintained or suppressed [ 5-81. In tolerant animals, i.e.…”

Suppressor Cells in Different Types of Unresponsiveness to Dinitrochlorobenzene (DNCB) Contact Sensitivity in Guinea Pigs

“…Specific immunological unresponsiveness to DNCB contact sensitivity in guinea pigs may be induced by an intraveneous injection of a high dose (500-600 mg/kg) of dinitrobenzenesulphonic acid sodium salt (DNBSO3) prior to (tolerance by pretreatment) [2] or at the time of the sensitizing attempt (tolerance during the primary response) [4]. Furthermore, a temporary specific unresponsiveness was achieved even in already sensitized animals by the same tolerogenic procedure (desensitization) [3].…”

Studies of Contact Hypersensitivity and Tolerance <i>in vivo</i> and <i>in vitro</i>

“…Although the above phe nomena are easily reproduced with DNCB and related chemicals like picryl chloride (PCI), there is no agreement regarding the mechanisms of the reactions involved. It was formerly inferred, from in vivo experi ments in animals, that tolerance of the above type was brought about by a central lack of responsiveness [2,5]; however, there have been recent indications of other possible mechanisms involving suppressor cells [1,13,21,26].…”