Antibody to the ligand of CD40, gp39, blocks the occurrence of the acute and chronic forms of graft-vs-host disease.
Antibody to the ligand of CD40, gp39, blocks the occurrence of the acute and chronic forms of graft-vs-host disease.
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DOI：
10.1172/jci117453
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发表时间：
1994-09
期刊：
影响因子：
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通讯作者：
F. H. Durie;A. Aruffo;J. Ledbetter;K. M. Crassi;W. Green;L. Fast;R. Noelle
中科院分区：
文献类型：
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作者：
F. H. Durie;A. Aruffo;J. Ledbetter;K. M. Crassi;W. Green;L. Fast;R. Noelle
慢性和急性移植物抗宿主病（cGVHD和aGVHD）是由供体细胞对宿主不同的MHC等位基因产生应答引起的。在cGVHD（H-2d-->H-2bd）中，多克隆免疫球蛋白产生的增加是由于供体同种异体特异性辅助T细胞（Th）和宿主B细胞的相互作用。体内给予CD 40配体gp 39的抗体可阻断cGVHD诱导的血清抗DNA自身抗体、IgE产生、体外自发免疫球蛋白产生和相关的脾肿大。在终止抗gp 39给药后，抗体产生仍被抑制很长一段时间。在GVHD中诱导的抗同种异体CTL应答也通过体内施用抗gp 39来预防，因为相关的脾肿大也是如此。这些数据表明，CD 40-gp 39相互作用是关键的GVHD和CD 40-gp 39可能是一个有价值的配体-受体对靶向免疫抑制剂，以控制GVHD。
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.