Production of an antigen-specific component of suppressor inducer factor by a helper T-cell clone: Possible role for IL-1 at the interface of immunity and tolerance

When immunological homeostasis is disrupted by the introduction of substances which cannot be accommodated as 'self', a dynamic cellular interaction of the immune system ensues which may result in a positive state (immune response with subsequent memory) or in a negative one (immune unresponsiveness with subsequent tolerance). While much is known about both positive and negative states of immune function, relatively little work has focused upon the precise mechanisms of the decision-making process. We have examined the potential roles of IL-1 in this process. Using a well defined helper T-cell clone (D10.G4.1) and antigen-pulsed splenic adherent cells we have found that a number of agents which block the induction or action of IL-1 (ultraviolet irradiation of APC, addition of cyclosporin A, addition of anti-L3T4 antibody) resulted in the production, by the clone, of an antigen-specific factor involved in the induction of a suppressor T-cell circuit. This factor showed the same antigenic specificity as the helper cell (which is normally specific for antigen plus self Ia), and resembled by form and function a number of well characterized antigen-specific suppressor inducer molecules. Crude preparations containing IL-1 prevented the appearance of this suppressor inducer factor. These observations underline the pivotal role of the APC-helper T-cell interaction in determining, in part, whether immunity or suppression will follow exposure to an antigen and thus, the immunoregulatory outcome of an antigenic challenge.