The induction of carrier-specific helper cell tolerance in presensitized rats

Abstract

Lewis rats rendered tolerant to sheep IgG (SGG) show a markedly reduced antibody response to the 2,4,6-trinitrophenyl (TNP) hapten when later challenged with TNP-SGG. We have previously shown that this effect is due to functional unresponsiveness in the carrier SGG-specific helper T cell population. In this paper we demonstrate that induced helper cell tolerance is also maintained through a secondary immunogenic challenge. Furthermore, rats which are primed to the carrier SGG prior to tolerance induction also show a markedly reduced anti-TNP response upon secondary immunogenic challenge with TNP-SGG. The ability to specifically suppress a secondary response in this manner was found to be relatively long lasting, since rats showed reduced responsiveness when the secondary challenge was delayed for up to 4 weeks after tolerance induction. In addition, rats primed to the hapten (TNP) prior to carrier (SGG) tolerance induction also showed a marked reduction in anti-TNP antibody following challenge with TNP-SGG. These findings imply that helper cell tolerance can be induced in rats even after priming of carrier-specific (SGG) helper cells, or hapten-specific (TNP) B cells. These results parallel our other published findings that IgE responses in presensitized rats can be overcome by helper cell tolerance.