Development of Immunity and the Concept of Stem Cell Tolerance

Abstract

synopsis. Evidence is presented which indicates that differentiation of immunocompetence is achieved early in development, with some aspects of the immune system maturing concomitant with the appearance of blood-borne cells and thymic lymphocytes. Experi? ments are described which show that long-lasting, serum-mediated unresponsiveness to heterologous erythrocytes can be induced by injection of soluble factors released from such erythrocytes. These two lines of investigation lead to the hypothesis that tolerance may be achieved during development by the release, from various stem cells, of soluble factors which induce in the developing embryo a series of blocking factors. These factors subsequently are effective in preventing immune recognition not only of the stem cells themselves but also of their differentiated progeny. One of the most intriguing problems of developmental biology concerns the on? togeny of self-recognition. The concepts of immunological tolerance as originally de? veloped more than a decade ago (see Bur? net, 1959; Medawar, 1960) were largely based on the assumption that the embryo, during its development, must learn to distinguish self from not self, since subsequent immune reactions would otherwise lead to autoimmune destruction. A formidable body of experimental observations confirmed the basic validity of the concept of tolerance as an epigenetic developmental event (see Burnet, 1969, for historical overview).