Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution
Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution
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DOI：
10.1182/blood.v99.7.2586
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发表时间：
2002-04-01
期刊：
影响因子：
20.3
通讯作者：
Russell, NH
中科院分区：
文献类型：
--
作者：
Klangsinsirikul, P;Carter, GI;Russell, NH
移植物抗宿主病(GVHD)是异基因移植后的主要并发症，抗CD52的CamPath单抗可以消除GVHD。急性移植物抗宿主病(GVHD)的诱导需要宿主抗原通过抗原提呈细胞(APC)递呈给供者T细胞。最近的证据表明，在GVHD的诱导过程中，只有宿主APC才能与供体T细胞相互作用。由于CD52已被报道在DC上表达，我们推测移植前CamPath-1G除了对供者T细胞有任何影响外，还可能对循环中的DC有直接影响。通过直接免疫染色，我们证实了CD52在DC上的表达以及CamPath-1G在体外对纯化的DC的杀伤作用。在体内，Camath也耗尽了DC。在第一剂Camath-1G的24小时后，循环DC平均减少了79%(范围为44%-96%)。在接受CAMPATH-1G和放化疗处理5次后的第0天，9例患者中有7例检测不到DC，而在7例未接受CAMPATH-1G的条件化治疗的患者中，有6例仍然可以检测到宿主DC。CAMPATH-1G对移植后循环DC的重建无明显影响，且两组Dc1(CD11c(+))恢复较DC2(CD11c(-))快。嵌合体分析证实，接受Camath-1G的患者移植后恢复的DC来自供者来源。我们得出结论，在体内，Camath-1G导致宿主循环DC迅速耗尽，这可能在一定程度上解释了急性GVHD发生率较低的原因。供者DC的重建没有延迟，这可能对保存免疫重建很重要。(C)美国血液学学会2002年。
Graft-versus-host disease (GVHD), a major complication after allogeneic transplantation, can be abrogated by the Campath (anti-CD52) monoclonal antibody. The induction of acute GVHD requires host antigens to be presented to donor T cells by antigen-presenting cells (APCs). Recent evidence has suggested that only host APCs can interact with donor T cells in the induction of GVHD. Because CD52 has been reported to be expressed on DCs, we reasoned that pretransplant Campath-1G might have a direct effect on circulating DCs in addition to any effects on donor T cells. Using direct immuno-staining, we demonstrated expression of CD52 on DCs and that Campath-1G killed purified DCs in vitro. In vivo Campath also depleted DCs. Twenty-four hours after the first dose of Campath-1 G, circulating DCs were reduced by a mean of 79% (range, 44%-96%). By day 0 after 5 doses of Campath-1G and chemoradiotherapy conditioning, DCs became undetectable in 7 of 9 cases, whereas in 6 of 7 patients receiving conditioning therapy without Campath-1G, host DCs were still detectable. The reconstitution of circulating DCs after transplantation was not affected by Campath-1G and in both groups DC1 (CD11c(+)) recovered more rapidly than DC2 (CD11c(-)). Analysis of chimerism confirmed that the DCs recovering after transplantation in patients receiving Campath-1G were of donor origin. We conclude that in vivo Campath-1 G causes a rapid depletion of host circulating DCs and that this may, in part, explain the low incidence of acute GVHD. The reconstitution of donor DCs was not delayed, which may be important in preserving immune reconstitution.(C) 2002 by The American Society of Hematology.