Antilymphocytic antibodies and marrow transplantation. VII. Two of nine monoclonal anti-Thy-1 antibodies used for pretreatment of donor marrow suppressed graft-versus-host reactions without added complement.
Thierfelder S., Cobbold S., Kummer U., Waldmann H., Schuh R.
Eleven monoclonal antibodies of rat or mouse origin against the mouse pan T antigen Thy-1 were compared for their ability to reduce mortality from graft-versus-host disease (GVHD) when incubated with donor marrow. Spleen and bone marrow cells were transferred to F1 hybrids or to fully allogeneic (H-2 I-A incompatible) mice. Particular attention was paid to whether complement (rabbit) enhanced the anti-GVHD effect of the antibodies in homozygous histoincompatible chimeras: without complement, 5 IgM anti-Thy-1 and 2 IgG2a anti-Thy-1 did not reduce GVHD. With complement, acute GVHD was completely suppressed. Two of two rat IgG2b anti-Thy-1, however, suppressed acute GVHD without the need for added complement. One of the two also prevented chronic mortality following two haplotype-unmatched transplantation. This antibody, in contrast to other complement-fixing anti-Thy-1 antibodies, had previously been shown to delay rejection of skin allografts. Its specificity did not differ from other complement-dependent Thy-1 antibodies when tested in a cross-blocking radioimmunoassay, and it also had the lower affinity for Thy-1. It seems therefore that only a minority of the antibodies were able to fully exploit the marrow recipients' opsonizing capacity for suppression of GVHD. The important clinical implications of the remarkable difference in immunosuppression of various monoclonal antibodies with comparable specificity and capacity to fix complement in vitro are discussed.