ANTIBODY TO THE LIGAND OF CD40, GP39, BLOCKS THE OCCURRENCE OF THE ACUTE AND CHRONIC FORMS OF GRAFT-VS-HOST DISEASE

Chronic and acute graft-versus-host disease (cGVHD and aGVHD) result f rom donor cells responding to host disparate MHC alleles. In cGVHD (H- 2(d) --> H-2(bd)), heightened polyclonal immunoglobulin production is due to the interaction of donor allospecific helper T cells (Th) and t he host B cells. In vivo administration of antibody to the ligand for CD40, gp39, blocked cGVHD-induced serum anti-DNA autoantibodies, IgE p roduction, spontaneous immunoglobulin production in vitro, and associa ted splenomegaly. Antibody production remained inhibited for extended periods of time after termination of anti-gp39 administration. Anti-al logeneic CTL responses induced in aGVHD were also prevented by the in vivo administration of anti-gp39 as was the associated splenomegaly. T hese data suggest that CD40-gp39 interactions are critical in GVHD and that CD40-gp39 may be a valuable ligand-receptor pair for targeting i mmunotherapeutic agents to control GVHD.