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 disparate MHC alleles. In cGVHD (H-2d-->H-2bd), heightened polyclonal immunoglobulin production is due to the interaction of donor allospecific 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 autoantibodies, 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. Antiallogeneic CTL responses induced in a GVHD were also prevented by the in vivo administration of anti-gp39 as was the associated splenomegaly. These data suggest that CD40-gp39 interactions are critical in GVHD and that CD40-gp39 may be a valuable ligand-receptor pair for targeting immunotherapeutic agents to control GVHD.
Durie
F H
FH
Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756.
Aruffo
A
A
Ledbetter
J
J
Crassi
K M
KM
Green
W R
WR
Fast
L D
LD
Noelle
R J
RJ
D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000494:pharmacology* / Q000627:therapeutic use; D000917:Antibody Formation; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D019013:CD40 Antigens; D002908:Chronic Disease; D003433:Crosses, Genetic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D013154:Spleen / Q000637:transplantation
D000906:Antibodies; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007132:Immunoglobulin Isotypes; D007073:Immunoglobulin E