Immunological Unresponsiveness to Heterologous Serum Albumins in Adult Mice: Effect of Antigen Quality on Tolerogenicity

Abstract

STUDIES of experimental tissue transplantation have revealed that tolerance to transplantation antigens is more easily achieved across weak histocompatibility barriers than across strong ones^1–4. Also, the degree of foreignness between donor and recipient determines the results obtained in clinical transplantations^5–7. Taxonomic origin and thus the immunogenicity of red blood cells are important in producing drug-induced immunological unresponsiveness to heterologous erythrocytes in adult mice^8,9. In experimental work on tolerance to heterologous serum proteins the degree of dissimilarity between antigens and “self”-constituents has only rarely been considered. A study by Tempelis revealed that in chicks comparatively smaller amounts of an avian than of a mammalian serum protein were needed to induce a state of immunological tolerance. Furthermore, turkey globulin was more effective in producing unresponsiveness than globulin obtained from the goose¹⁰. The following hypothesis might thus be put forward: the smaller the phylogenetic disparity between the species from which the antigen is obtained and the experimental animal, the greater will be the tolerogenicity of the antigen in question. I have tested this hypothesis by assessing in adult mice tolerogenic properties of serum albumins obtained from species either closely related to the mouse or from species taxonomically more distant.