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PMID: 7521888 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Antibody to the ligand of CD40, gp39, blocks the occurrence of the acute and chronic forms of graft-vs-host disease.

The Journal of clinical investigation ·Vol. 94 ·No. 3 ·1994-09-00 ·Pages 1333-8

Durie FH, Aruffo A, Ledbetter J, Crassi KM, Green WR, Fast LD, Noelle RJ

Abstract

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.

MeSH Terms
Acute Disease Animals Antibodies/pharmacology,therapeutic use Antibody Formation Antigens, CD/immunology Antigens, Differentiation, B-Lymphocyte/immunology CD40 Antigens Chronic Disease Crosses, Genetic Enzyme-Linked Immunosorbent Assay Female Graft vs Host Disease/immunology,prevention & control Immunoglobulin E/blood,immunology Immunoglobulin Isotypes/analysis Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Inbred Strains Spleen/transplantation
Chemicals
Antibodies Antigens, CD Antigens, Differentiation, B-Lymphocyte CD40 Antigens Immunoglobulin Isotypes Immunoglobulin E
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Durie F H
Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756.
Aruffo A
Ledbetter J
Crassi K M
Green W R
Fast L D
Noelle R J
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI117453
Published
1994-09-00
Pages
1333-8
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC295220
Subset
IM
Grants
PHS HHS · A-126296 · United States
NCI NIH HHS · CA-23108 · United States
NCI NIH HHS · CA-36860 · United States
External Links
PubMed source DOI: 10.1172/JCI117453 PMC Full Text View journal details
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