Antigen “Suicide”: A Preliminary Study on the Induction of Specific Anti-Immunoglobulin Immunological Suppression in Vivo, Using Radiolabeled Immunoglobulin as “Lethal” Antigen

Abstract

The effectiveness of immunodiagnosis and immunotherapy is limited when xenogeneic antibodies are used, due to the host's anti-immunoglobulin response. We have attempted to specifically suppress the immune response to the immunogen (immunoglobulin) administered. The concept of antigen “suicide” was used, where the antigen (immunoglobulin) was suitably radiolabelled and administered to animals. The question asked was whether immunocompetent cells that specifically interact with the radiolabeled immunogen, would be lethally irradiated and thus become inactivated rather than stimulated. When mice where primed with 111Indium-labelled polyclonal human IgG (specific activity 15 mCi/mg), they responded 13% less than control animals (p = 0.0485). This suppression was IgG-specific, since all animals responded similarly to a control antigen (human albumin). However, a second boost of the same 111Indium-labelled preparation (specific activity 7 mCi/mg) did not show any statistically significant immunosuppression. In addition, rabbits primed with125 Iodine-labelled mouse monoclonal antibody (specific activity 180mCi/mg) and boosted with the same unlabelled monoclonal antibody, showed a similar anti-mouse antibody response with the ones that received only unlabelled preparation twice. We conclude that the concept of antigen “suicide” may be effective for the induction of specific unresponsiveness; when immunoglobulins are radiolabeled with 111Indium at high specific activities, the desired state of specific immune suppression may be induced.