Specific unresponsiveness to transplantation antigens induced by auto-immunisation with syngeneic, antigen-specific T lymphoblasts

Abstract

AUTOIMMUNE reactions have hitherto been considered to be harmful or at best neutral for the individual. Specific autoimmune reactions in certain experimental systems may, however, have consequences of potential positive value for the, individual¹. Here, advantage was taken of the fact that antigen-binding receptors of B and T lymphocytes belong to the classes of self-molecules against which autoimmunity can be inflicted^1–4. Such receptors can be classified according to specific antigen-binding capacity or unique antigenic, idiotypic markers⁵. In one system studied, autoanti-idiotypic antibodies were induced against rat T and B cell receptors specific for major histocompatibility antigens of the species¹. Soluble antigen-binding receptors were purified using anti-idiotype immunosorbants. Autoimmunisation with purified, polymerised receptors lead to production of autoanti-idiotype immunity. This caused a selective elimination of lymphocytes carrying the relevant idiotypic, antigen-binding receptors. Consequently, such autoimmune rats could be shown to be tolerant to transplantation of skin from the proper foreign donor, whereas reactivity against third party skin was left intact. No negative side-effects were noted during immunisation. Thus, autoimmunisation against the individual's receptors for a given antigen may constitute an efficient way of producing specific immune tolerance in adult, immunocompetent individuals. This approach would have obvious possible applications in clinical transplantation immunology, in treatment of allergic disorders, and might even be used when trying to regulate the course of certain autoimmune diseases. The requirement to have accessible anti-idiotypic antibodies to make the necessary immunosorbants to obtain pure receptors, is, however, a severe drawback. An approach allowing autoanti-receptor immunisation without having to rely on sophisticated or unobtainable reagents would be of great usefulness. Here, we report on a technique whereby autoanti-receptor immunity leading to specific immune unresponsiveness can be induced in vivo using as immunogen the individual's own antigen-specific lymphoblasts as obtained after in vitro immunisation.