PREVENTION OF THE HUMORAL RESPONSE INDUCED BY AN ANTI-CD3 MONOCLONAL-ANTIBODY BY DEOXYSPERGUALIN IN A MURINE MODEL

Multiple treatments with the potent immunosuppressant murine antihuman CD3 mAb OKT3 is sometimes precluded by the onset of a neutralizing hu moral response mostly consisting of anti-idiotypic antibodies. A hamst er antimurine CD3 monoclonal Ab, 145-2C11, shares many properties with OKT3, in particular the ability to induce a strong Ab response in mic e. Deoxyspergualin (DSG), a metabolite of the antibiotic spergualin, h as been shown to reduce Ab production triggered by pathogens in a vari ety of infectious models and against common antigens. In this study, w e examined the ability of DSG to inhibit the humoral response induced by 145-2C11. DSG prevented the Ab production triggered by the anti-CD3 mAb in an Ag-specific manner and significantly reduced the Ab product ion in mice previously primed with 145-2C11. We showed that DSG had a long-term effect on B cells and a transient effect on T cells. In effe ct, DSG was found to induce a prolonged Ag-specific unresponsiveness o f B lymphocytes, and to transiently reduce the capacity of T lymphocyt es to deliver help to B cells, in part by reducing IL-4 production. DS G did not reduce the immunosuppressive properties of the anti-CD3 mAb. In fact, the combination of DSG with 145-2C11 prolonged the survival of allogeneic skin grafts when compared with the administration of 145 -2C11 or DSG alone. Thus, the coadministration of DSG with OKT3 may be of clinical interest to reduce the humoral response triggered by the mAb.