REGULATION OF AUTOSENSIT IZAT ION THE IMlVIUNE ACTIVATION AND SPECIFIC INHIBITION OF SELF-RECOGNIZING THYMus-DERIVED LYMPtIOCYTES*

Natural tolerance to self-antigens is a haUmark of the immune system. The mech-anism by which self-tolerance is maintained may shed light upon the pathogenesls of autoimmune diseases as well as on the development of the immune system itself. Thus, the question of the cellular basis of self-tolerance has both practical and theoretical importance. The nonreactivity of the immune system to self-antigens could be attributed to either of two basic mechanisms. Potentially self-reactive lymphocytes might be eliminated, or such lymphocytes might exist in a state of tolerance. The concept hat potentially self-reactive lymphocytes are eliminated uring development has been clearly outlined by Burnet. According to the elimination theory, autoimmune diseases occur because of the appearance of "forbidden clones " of immunocompetent lympho-cytes that can recognize self-antigens. These forbidden clones can arise by somatic mutation of lymphocytes, orby contact of lymphocytes with self-antigens which were not accessible to the immune system during its development (1). Jerne has used the concept of lymphocyte limination in an attempt to explain the generation of lympho