Immunologic tolerance, the phenomenon whereby antigen interacts with the lymphoid system to impair its later capacity to respond to that antigen, remains one of the most fascinating problems in cellular immunology. The capacity of individuals to discriminate" self" from" not self" has assumed a new dimension since the realization that T lymphocytes only see foreign antigens in the context of" self" molecules of the major histocompatibility complex (MHC)(131), and so the newer field of MHC restriction has become intertwined with immunologic tolerance and indeed with allaspects of immunoregulation. Although the central interest of students of im munologic tolerance lies in the establishment and maintenance of self recognition, experimental realities mandate that most work on tolerance in fact is performed with model systems where foreign antigens, rather than autologous constituents, are presented to the lymphoid system to induce a state of non-reactivity. It then becomes a matter of considerable difficulty to judge whether the effects observed mimic the physiological situation of lymphocytes coming to grips with the need to avoid horror aulotoxicus, or whether the model illustrates some facet of immunoregulation needed to limit the cascade of immunoproliferation that follows the introduction of antigen.

Faced with this constraint, investigators of immunologic tolerance fall into three groups. The first, numerically the largest, describes particular model systems and refrains from speculation as to how major a role the cellular mechanism revealed by the study plays in physiological self-recog nition. Some members of this group form a" tolerance is dead" subgroup, who believe nothing is all that special about self antigens, and that the avoidance of autoimmunity depends on myriad immunoreguiatory and