Effect of the YCD3-1 anti-mouse monoclonal on murine GvHD.

ABSTRACT

The potential for applying the YCD3-1 rat-anti-mouse IgG2b anti-CD3-epsilon monoclonal antibody (MAB) to the study of graft-versus-host disease (GvHD) in mouse models has been examined. This MAB, unlike the previously developed hamster-anti-mouse-CD3 MABs, had been reported to exhibit strong cytolytic properties when applied in vitro in the presence of complement. Therefore, it was of interest to determine whether it could be effectively used for T-cell depletion in mice to suppress GvHD in the same manner as the anti-human-CD3 MABs have been applied in clinical transplantation. Evaluation of the effectiveness of this antibody was carried out both under fully allogeneic MHC-mismatched and under unrelated-donor MHC-matched marrow transplant conditions. For both types of transplantation, depletion of the donor cells with YCD3-1 plus complement prior to their injection into lethally irradiated recipients significantly suppressed GvHD, resulting in survivals of 75-79%, as compared to 8-13% in the controls that received undepleted cells from the same donors (p < 0.0001). These results suggest that the YCD3-1 MAB may have a potential for use as a negative selection agent in the further definition of the roles of the various T-cell subtypes, as well as the possible roles of natural-killer cells, in future studies into the mechanisms of GvHD, and of the graft-versus-leukemia effect.