Further Development of the Mathematical Model of Immunological Tolerance

Abstract

Our mathematical model of immunological tolerance to human serum albumin (HSA) in chickens [1, 2] was formulated on experimental evidence suggesting that the major mechanism underlying the inhibition of anti-HSA antibody production in tolerant chickens was Β cell tolerance [3, 4]. The relevant experiments were carried out in chickens of homogeneous inbred lines and that made possible lymphoid cell transfers among the syngeneic experimental birds. The existence of suppressor cells induced in tolerant chickens was not proved by these cell transfers. This finding suggested a direct inhibition of immunocompetent cells (ICC) by the tolerizing administration of antigen. The inhibition was apparently irreversible, as escape from tolerance was not observed in the spleen cells of tolerant birds transferred to non-reactive recipients. In contrast to the situation in mammals tolerant to xenogeneic serum proteins, neonatal thymectomy did not detectably influence tolerance to HSA in chickens. On the other side, neonatal bursectomy increased and prolonged substantially the tolerance in chickens. From these and other findings we concluded that Τ cells do not play any substantial role in this tolerant state and that the major mechanism operating there is clonal deletion or irreversible inactiva-tion of Β lymphocytes.