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

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.