Bosma B M, Metselaar H J, Tra W M W, Mancham S, Kuipers E J, Tilanus H W, Kwekkeboom J
Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center, Rotterdam, The Netherlands.
Clin Exp Immunol. 2007 Sep;149(3):525-34. doi: 10.1111/j.1365-2249.2007.03449.x. Epub 2007 Jul 23.
The aim of the present study was to elucidate the impact of liver transplantation (LTX) on myeloid dendritic cell (MDC) homeostasis. We observed a threefold reduction of circulating CD1c(+) MDC immediately after LTX (n = 16; P < 0.01), and normalization between 3 and 12 months after LTX. This decline was not due to recruitment of MDC into the liver graft, as numbers of MDC in post-LTX liver graft biopsies were not increased compared to pre-LTX biopsies (n = 7). Moreover, no change in chemokine receptor expression on circulating MDC was observed, suggesting that their homing properties were not altered. Normalization of circulating MDC was associated with withdrawal of corticosteroid therapy, and not with changes in calcineurin inhibitor intake, indicating that corticosteroids are responsible for the observed changes in numbers of circulating MDC. During high-dose corticosteroid treatment early after LTX, circulating MDC showed a lowered maturation status with decreased expression of human leucocyte antigen D-related (HLA-DR) and CD86 compared to pre-LTX values (P < 0.01). However, when MDC from blood of LTX recipients were matured ex vivo, they up-regulated HLA-DR and co-stimulatory molecules to a comparable extent as MDC from healthy individuals. In addition, ex vivo matured MDC from both groups had equal allogeneic T cell stimulatory capacity. In conclusion, during the first months after LTX numbers and maturational status of circulating MDC are impaired significantly, probably due to a suppressive effect of corticosteroids on MDC. However, corticosteroid therapy does not imprint MDC with an intrinsic resistance to maturation stimuli.
本研究的目的是阐明肝移植(LTX)对髓样树突状细胞(MDC)稳态的影响。我们观察到LTX后即刻循环CD1c(+) MDC减少了三倍(n = 16;P < 0.01),并在LTX后3至12个月恢复正常。这种下降并非由于MDC募集到肝移植物中,因为与LTX前活检相比,LTX后肝移植物活检中的MDC数量并未增加(n = 7)。此外,未观察到循环MDC上趋化因子受体表达的变化,这表明它们的归巢特性未改变。循环MDC的恢复正常与皮质类固醇治疗的撤减有关,而与钙调神经磷酸酶抑制剂摄入量的变化无关,这表明皮质类固醇是循环MDC数量变化的原因所在。在LTX后早期进行大剂量皮质类固醇治疗期间,与LTX前的值相比,循环MDC显示出成熟状态降低,人类白细胞抗原D相关分子(HLA-DR)和CD86的表达减少(P < 0.01)。然而,当从LTX受者血液中分离的MDC在体外成熟时,它们上调HLA-DR和共刺激分子的程度与健康个体的MDC相当。此外,两组体外成熟的MDC具有同等的同种异体T细胞刺激能力。总之,在LTX后的最初几个月里,循环MDC数量和成熟状态受到显著损害,这可能是由于皮质类固醇对MDC的抑制作用。然而,皮质类固醇治疗并未使MDC对成熟刺激产生内在抗性。