Tolerance and bystander suppression, with involvment of CD25-positive cells, is induced in rats receiving serum from ovalbumin-fed donors

In the present study we have investigated if transfer of serum from rats fe d ovalbumin (OVA) leads to specific tolerance and bystander suppression in recipient animals. Rats that received serum from OVA-fed donors had a lower delayed-type hypersensitivity reaction (DTH) both against OVA and the byst ander antigen, human serum albumin (HSA), compared with recipients given se rum from control-fed animals. The in vitro proliferation of OVA- and HSA-st imulated spleen cells and the serum immunoglobulin G (IgG) antibody levels against OVA and HSA were also lower in the animals that received serum from OVA-fed animals compared with the controls. There was no reduction of the immune response to HSA if the recipient animals, given serum from OVA-fed d onors were immunized with OVA and HSA at separate sites. Depletion of CD25- positive cells from spleen suspensions from rats receiving serum from OVA-f ed animals, resulted in a significant increase in proliferation of OVA-stim ulated cells in vitro compared with the controls. Tolerogenic activity coul d be demonstrated, both in a fraction from serum containing structures smal ler than 100 000 MW and a fraction with components larger than 100 000 MW, compared with size-related serum fractions obtained from control-fed animal s. This implies that the tolerogenic activity could be mediated by more tha n one serum component. The tolerogenic activity was most prominent in anima ls receiving the larger size fraction with a more pronounced suppression of the DTH reaction and lower levels of IgG anti-OVA antibodies in serum comp ared with controls. A novel finding in the present study was that the trans fer of serum, collected from rats fed OVA, led to a reduction of the immune response to a bystander antigen in the recipients. This suggests that the induced tolerance is at least partly due to suppression. The suppression co uld have been mediated by CD25-positive cells since removal of these cells resulted in an increased in vitro proliferation against OVA.