Conversion of immunity to suppression by in vivo administration of I-A subregion-specific antibodies

The in vivo administration of antibodies specific for gene products of the I-A subregion represents an immunologically specific approach to the manipulation of Ly-1+ T cell responses to antigen. This has been demonstrated previously by the capacity of anti-I-A antibody treatment to abrogate T cell-mediated delayed-type hypersensitivity (DTH) responses to syngeneic tumor antigen, hapten, and non-H-2 histocompatibility antigens. Evidence obtained in these studies suggested that the primary action of antibody was related to its ability to interfere with macrophage-T cell interactions during antigen presentation, consistent with the demonstration that similar antibodies inhibit T cell binding to antigen-pulsed macrophages in vitro. Results presented in this report provide evidence for an additional consequence of in vivo antibody administration that may be secondary to any direct effects on I-A-restricted antigen presentation. Thus, animals treated with I-A subregion-specific antibodies also develop a population of antigen-specific suppressor T cells (Ts) capable of inhibiting recipient Ly-1+ T cell responses to tumor antigen. The induction of suppression appeared to be an essential component of the total biological activity of these antibodies, because elimination of Ts precursors by cyclophosphamide also abrogated the antibody-mediated inhibition of DTH responsiveness. These results are discussed with respect to the possible mechanisms of Ts activation by anti-I-A antibody administration, and the general applicability of this approach as a means of clinical immunotherapy to limit inappropriate T cell responses in human disease.