Klangsinsirikul Phennapha, Carter G Ian, Byrne Jennifer L, Hale Geoff, Russell Nigel H
Division of Haematology, School of Clinical Laboratory Sciences, University of Nottingham, City Hospital, Hucknall Road, Nottingham NG5 1PB, United Kingdom.
Blood. 2002 Apr 1;99(7):2586-91. doi: 10.1182/blood.v99.7.2586.
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 immunostaining, 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-1G, 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-1G 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.
移植物抗宿主病（GVHD）是同种异体移植后的一种主要并发症，抗淋巴细胞球蛋白（抗CD52）单克隆抗体可消除该病症。急性移植物抗宿主病的诱发需要抗原呈递细胞（APC）将宿主抗原呈递给供体T细胞。最近的证据表明，在移植物抗宿主病的诱发过程中，只有宿主抗原呈递细胞能够与供体T细胞相互作用。由于据报道CD52在树突状细胞（DC）上表达，我们推断移植前的抗淋巴细胞球蛋白1G（Campath-1G）除了对供体T细胞有任何作用外，可能对循环中的树突状细胞有直接影响。通过直接免疫染色，我们证明了CD52在树突状细胞上的表达，并且抗淋巴细胞球蛋白1G在体外杀死了纯化的树突状细胞。在体内，抗淋巴细胞球蛋白也使树突状细胞减少。在首次注射抗淋巴细胞球蛋白1G后24小时，循环中的树突状细胞平均减少了79%（范围为44%-96%）。在5次注射抗淋巴细胞球蛋白1G和放化疗预处理后到第0天，9例中有7例无法检测到树突状细胞，而在7例接受无抗淋巴细胞球蛋白1G预处理治疗的患者中，有6例仍可检测到宿主树突状细胞。移植后循环树突状细胞的重建不受抗淋巴细胞球蛋白1G的影响，并且两组中CD11c(+)的DC1比CD11c(-)的DC2恢复得更快。嵌合分析证实，接受抗淋巴细胞球蛋白1G治疗的患者移植后恢复的树突状细胞来自供体。我们得出结论，体内抗淋巴细胞球蛋白1G可导致宿主循环树突状细胞迅速减少，这可能部分解释了急性移植物抗宿主病的低发病率。供体树突状细胞的重建没有延迟，这在维持免疫重建中可能很重要。
