MODELS FOR ASSESSING THE EFFECT OF TOXICANTS ON IMMUNOCOMPETENCE IN MICE .2. EFFECT OF CYCLOPHOSPHAMIDE ON THE ANTIBODY-RESPONSES TO TYPE-III PNEUMOCOCCAL POLYSACCHARIDE AND TETANUS TOXOID IN BALB-C FEMALE MICE

  • 1 January 1978
    • journal article
    • research article
    • Vol. 1  (6) , 791-812
Abstract
A mixture of antigens was used to detect alterations in immunocompetence. Type III pneumococcal polysaccharide (S3) and tetanus toxoid (TT) stimulate different cellular components and can be used to assess different compartments of the immune mechanism. Cyclophosphamide (CP), a known immunosuppressant, had a potent effect upon the antibody [Ab] responses to S3 and TT. All doses of CP administered within 2 days of priming with S3 resulted in a dose-related immunosuppressive action which persisted even after re-injection of S3. CP 300 Sg/kg given up to 14 days prior to or following primary immunization resulted in a marked suppression of Ab to S3. Doses of S3 which were partially tolerogenic were made even more so by injections of CP. The effect persisted over a 96 day experimental period. CP suppressed the formation of memory cells necessary for induction of a secondary-type Ig[immunoglobulin]G response to TT. The time of injection for maximum suppression was days 10-14 after priming. The suppression must involve cellular mechanisms different from those responsible for S3 Ab suppression. There was a difference in the degree and persistence of the suppressive effect, since the suppressed animals were able to mount an immune response to subsequent injections of TT. Double injections of a high dose (300 mg/kg) of CP 4 wk after priming completely suppressed the acquired immunity to S3 and TT. Low and moderate doses of CP appeared to induce a mild augmentation of S3 Ab response when given 4 wk after priming. An immunosuppressive effect occurred if the primed animals were re-injected with S3 or challenged with TT within a period of 2 days prior to or after receiving the CP treatment. Doses of CP, injected prior to challenge and resulting in suppressed tetanus anti-toxin production, elevated the titers of specific IgE Ab. The class of antibody is associated with adverse hypersensitivity reactions. These data provided background for the development of models to assess immunocompetence in mice, based on a study of immune profiles following exposure to selected T[thymus-derived cell]-dependent and T cell-independent antigens. Such models may be used to detect potentially hazardous chemicals found in the environment or incorporated into foods, drugs or cosmetics.