Hyporesponsiveness to a GnRH vaccine in a non-responder mouse strain is T-cell mediated

Abstract

Immunization of rats and monkeys with the decapeptide gonadotropin releasing hormone (GnRH) linked to carriers such as diphtheria toxoid (DT) or tetanus toxoid (TT) results in a marked atrophy of the prostate. This vaccine is now being explored for its potential in the "immunosurgery" of prostatic hypertrophy in men and is currently undergoing Phase I/II clinical trials. We have been investigating immunogenetic aspects of immune responses to this hapten-carrier conjugate, and in a recent communication we described the responses of different strains of mice to GnRH conjugated to DT (GnRH-DT). Mice of the 129 (H-2^b) strain were found to be non-responders to GnRH. However, further immunization of GnRH-DT-immunized 129 mice with GnRH linked to an alternate carrier, TT, resulted in the production of high levels of anti-GnRH antibodies. This showed that 129 mice are not deficient in GnRH-specific B cells and that the lack of response to GnRH in 129 mice is possibly due to (i) the lack of appropriate helper T-cells or (ii) the presence of suppressor cells. In this report we present evidence to support the existence of suppressor cells in GnRH-DT-immunized 129 mice.