IMMUNOREGULATION IN FISH .2. INTERMOLECULAR-INDUCED SUPPRESSION OF ANTIBODY-RESPONSES STUDIED BY HAPTENATED ANTIGENS IN ATLANTIC SALMON (SALMO-SALAR L)
Jea. Killie et To. Jorgensen, IMMUNOREGULATION IN FISH .2. INTERMOLECULAR-INDUCED SUPPRESSION OF ANTIBODY-RESPONSES STUDIED BY HAPTENATED ANTIGENS IN ATLANTIC SALMON (SALMO-SALAR L), Developmental and comparative immunology, 19(5), 1995, pp. 389-404
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.