Rapid Publication 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 from donor cells responding to host dispa-rate MHC alleles. In cGVHD (H-2d-- H-2bd)), heightened polyclonal immunoglobulin production is due to the interac-tion of donor allospecffic helper T cells (Th) and the host B cells. In vivo administration of antibody to the ligand for CD40, gp39, blocked cGVHD-induced serum anti-DNA au-toantibodies, IgE production, spontaneous immunoglobulin production in vitro, and associated splenomegaly. Antibody production remained inhibited for extended periods of time after termination of anti-gp39 administration. Antialloge-neic CTL responses induced in aGVHD were also prevented by the in vivo administration of anti-gp39 as was the associ-ated splenomegaly. These data suggest that CD40-gp39 in-teractions are critical in GVHD and that CD40-gp39 may be a valuable ligand-receptor pair for targeting immuno