IMMUNOREGULATION IN FISH .2. INTERMOLECULAR-INDUCED SUPPRESSION OF ANTIBODY-RESPONSES STUDIED BY HAPTENATED ANTIGENS IN ATLANTIC SALMON (SALMO-SALAR L)

Here we report evidence for T cell dependent intermoIecular-induced su ppression of antibody responses in fish, using a panel of T cell depen dent (TD) and T cell independent (TI) hapten-carrier antigens. Atlanti c salmon were immunized intraperitoneally either with protein antigens : Limulus polyphemus hemocyanin (LPH), chicken gammaglobulin (CGG), A. salmonicida surface A-layer protein (ALP(Asal)) or lipopolysaccharide (LPS) antigens isolated from A. salmonicida and Eseherichia coil. The various antigens were given as a mixture of the native and haptenated (4-hydroxy-3-iodo-5-nitrophenyl-acetic acid, NIP; 2,4,6-trinitropheny l-acetic acid, TNP; fluorescein-5-iso-thiocyanate, FITC) forms. The sa lmon immune system responded to the antigen mixtures by eliciting high anti-hapten titers whereas the antibody titers against protein determ inants were low (suppress 65-95%) as determined by ELISA. The suppress ion was induced between haptens (NIP and FITC) and between heterologou s antigens (NIP-CGG and LPH) indicating that the mechanisms involved w ere non-specific. Moreover, suppression was induced by TD antigens onl y, indicating that the mechanism was T cell dependent. Injection of an tigen mixtures containing variable amounts of the competing antigens s howed that the kinetics of suppression was dose-ratio and dose depende nt. In a timecourse study it was found that the suppressed anti-LPH re sponse was unchanged until native LPH was injected almost 2 years afte r the primary immunization, showing that permanent tolerance had not b een induced. Sequential immunization showed that the antibody response was most sensitive to suppression during the initial 10 days after im munization. Moreover, the carrier antigen was also able to induce supp ression of hapten epitopes, but only if the anti-carrier response was allowed to develop for 14 days before the hapten-carrier antigen was i njected. This shows that AIS in fish is elicited as a result of the im mune response to the dominant antigen, and can be induced against eith er antigens if the temporal order of administration is reversed. A pos sible model for AIS as a normal immunoregulatory process in fish is pr oposed and discussed.