Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
Pediatric Blood and Marrow Transplantation Program, Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Biol Blood Marrow Transplant. 2019 Apr;25(4):819-826. doi: 10.1016/j.bbmt.2018.10.013. Epub 2018 Oct 23.
Innate immune cells are the first to recover after allogeneic hematopoietic cell transplantation (HCT). Nevertheless, reports of innate immune cell recovery and their relation to adaptive recovery after HCT are largely lacking. Especially predicting CD4 T cell reconstitution is of clinical interest, because this parameter directly associates with survival chances after HCT. We evaluated whether innate recovery relates to CD4 T cell reconstitution probability and investigated differences between innate recovery after cord blood transplantation (CBT) and bone marrow transplantation (BMT). We developed a multivariate, combined nonlinear mixed-effects model for monocytes, neutrophils, and natural killer (NK) cell recovery after transplantation. A total of 205 patients undergoing a first HCT (76 BMT, 129 CBT) between 2007 and 2016 were included. The median age was 7.3years (range, .16 to 23). Innate recovery was highly associated with CD4 T cell reconstitution probability (P < .001) in multivariate analysis correcting for covariates. Monocyte (P < .001), neutrophil (P < .001), and NK cell (P < .001) recovery reached higher levels during the first 200days after CBT compared with BMT. The higher innate recovery after CBT may be explained by increased proliferation capacity (measured by Ki-67 expression) of innate cells in CB grafts compared with BM grafts (P = .041) and of innate cells in vivo after CBT compared with BMT (P = .048). At an individual level, patients with increased innate recovery after either CBT or BMT had received grafts with higher proliferating innate cells (CB; P = .004, BM; P = .01, respectively). Our findings implicate the use of early innate immune monitoring to predict the chance of CD4 T cell reconstitution after HCT, with respect to higher innate recovery after CBT compared with BMT.
固有免疫细胞是异基因造血细胞移植（HCT）后最早恢复的细胞。然而，关于固有免疫细胞恢复及其与 HCT 后适应性恢复的关系的报告在很大程度上仍然缺乏。特别是预测 CD4 T 细胞重建具有临床意义，因为该参数与 HCT 后生存机会直接相关。我们评估了固有恢复是否与 CD4 T 细胞重建概率有关，并研究了脐带血移植（CBT）和骨髓移植（BMT）后固有恢复之间的差异。我们开发了一个用于移植后单核细胞、中性粒细胞和自然杀伤（NK）细胞恢复的多变量、联合非线性混合效应模型。共有 205 例于 2007 年至 2016 年间接受首次 HCT（76 例 BMT，129 例 CBT）的患者纳入研究。中位年龄为 7.3 岁（范围，0.16 至 23 岁）。在调整协变量的多变量分析中，固有恢复与 CD4 T 细胞重建概率高度相关（P<0.001）。与 BMT 相比，CBT 后前 200 天固有细胞（单核细胞、中性粒细胞和 NK 细胞）恢复达到更高水平（P<0.001）。CBT 后固有恢复较高可能是由于 CB 移植物中的固有细胞（与 BM 移植物相比，P=0.041）和 CBT 后体内的固有细胞（与 BMT 相比，P=0.048）增殖能力增加所致。在个体水平上，无论是 CBT 还是 BMT 后固有恢复增加的患者，其接受的移植物中具有更高增殖能力的固有细胞（CB；P=0.004，BM；P=0.01）。我们的研究结果表明，使用早期固有免疫监测来预测 HCT 后 CD4 T 细胞重建的机会，与 CBT 后相比，BMT 后固有恢复更高。
