Significance and mechanisms of cellular regulation of the immune response.

The conditions known to favor the induction of delayed-type hypersensitivity (DTH), IgM and IgG antibody production, can be accounted for on the postulate that their precursors require the formation of different numbers of inductive complexes between their receptors, antigen, and the antigen-specific factor derived from helper T cells. The postulate that DTH precursors require the least, IgM B cells an intermediate number, and IgG precursors the most, accounts for the following facts: i) antigens with few foreign sites, for which there are relatively few helper T cell clones, induce only DTH; ii) medium doses of antigens that bear many foreign sites induce a humoral response; whereas iii) low doses that do not result in efficient collaboration induce DTH; and iv) high doses that partially block collaboration also lead to the induction of DTH. Furthermore, the conditions under which unresponsiveness can be induced at the humoral level in immunological competent animals are just those that give rise to the induction of DTH; the induction of a humoral response is also known to result in unresponsiveness at the DTH level. Therefore it seems very likely that these unresponsive states reflect the cellular regulation responsible for the exclusiveness between the induction of DTH and humoral immunity observed in the whole animal. Theoretically, this exclusiveness is due to the action of regulatory T cells. The biological significance of the way in which the induction of different classes is regulated is discussed. Experimental evidence is described that tests the following predictions: i) the class of response induced is due to the action of suppressor and repressor T cells, and ii) it is the number of inductive complexes formed that determines the class of response induced; DTH precursors require the least number and IgG precursors the most.