Suppression of BCG cell wall-induced delayed-type hypersensitivity by pretreatment with killed BCG: induction of nonspecific suppressor T cells by the adjuvant portion (MDP) and of specific suppressor T cells by the antigen portion (TAP)

Abstract

We showed previously that antigen-nonspecific suppressor T cells induced by i.v. injection of heat-killed bacillus Calmette-Guérin (BCG) were involved in suppression of delayed-type hypersensitivity (DTH). We suggested that the adjuvant portion of BCG might be involved in the induction of these cells. In this report, we show that BCG cell wall-induced DTH responses in mice pretreated with muramyl dipeptide (MDP), a minimum adjuvant constituent of BCG, were suppressed nonspecifically. In addition, we show that pretreatment with tuberculin active peptide (TAP), the antigenic peptide from Mycobacterium tuberculosis, induces antigen-specific suppression of DTH responses. In both instances, suppression was shown to be due to non-adherent cells that act to inhibit elicitation of DTH. Furthermore, using the macrophage migration inhibition assay, an in vitro correlate of DTH, we found that antigen-nonspecific and antigen-specific suppressor T cells were induced by the injection of MDP and TAP, respectively. Thus, suppressor T cells induced by the adjuvant and antigen portions of BCG may act by interfering with the lymphokine-dependent mechanisms by which DTH effector T cells elicit DTH.