The potential of patients' peripheral blood mononuclear cells to differentiate into dendritic cells after hematopoietic stem cell transplantation Hironori Yoshino a , Naoki Watanabe a , Kenji Takahashi a, b , Kazuto Ogura c , Tomoaki Akagi c , Kohmei Kubo c , Ikuo Kashiwakura a, ⁎ a Department of Radiological Life Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, Aomori 036-8564, Japan b Department of Veterinary Pharmacology, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan c Department of Hematology, Aomori Prefectural Central Hospital, Aomori 030-8553, Japan abstract article info Article history: Received 6 May 2011 Accepted 3 October 2011 Available online 20 October 2011 Keywords: Immune reconstitution Dendritic cell Hematopoietic stem cell transplantation Aims: Although hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hema- tological disorders, there is persistent immunosuppression in both allogeneic and autologous HSCT. Dendritic cells (DCs) play key roles in the immune system. This study investigated whether the DC progenitor cells within patients' peripheral blood after HSCT have the potential to differentiate into DCs. Main methods: Twenty-eight patients were included in this study, and peripheral blood samples were ba- sically taken before starting the conditioning regimen, on the day of transplantation (day 0), and on days + 14, + 28, + 42, + 70 and + 170 after transplantation. Immature DCs (iDCs) were induced from adherent mononuclear cells by using recombinant human granulocyte-macrophage colony-stimulating factor plus interleukin-4. Key findings: The iDCs expressed cell surface antigens such as CD40 and HLA-DR, and they had phagocytotic activity, thus showing the characteristics of iDCs. The induction of iDCs was possible from day +14 after HSCT. However, there were differences between allogeneic and autologous HSCT in the expression of CCR5 in iDCs at day +14 after transplantation. Furthermore, the up-regulation of maturation-related an- tigens by maturation stimuli was higher after HSCT compared with before HSCT. Significance: We demonstrated that patients' peripheral blood mononuclear cells have the potential to dif- ferentiate into DCs beginning on day +14 after HSCT, although some differences exist between allogeneic and autologous HSCT and between before and after HSCT. © 2011 Elsevier Inc. All rights reserved. Introduction Hematopoietic stem cell transplantation (HSCT) is well estab- lished as a curative treatment for many hematological malignancies and some non-malignant disorders. Donor-derived hematopoietic stem cells are used for the reconstitution of immune function after ra- diation and/or chemotherapy. However, it is well-recognized that there is persistent immunosuppression after both allogeneic and au- tologous HSCT, because humoral and cellular immunity may take a year or more to return to normal (Guillame et al., 1998). Therefore, the risk of infectious complications follows transplantation and lasts for more than a year. Acute graft-versus host disease (GVHD) is a lethal complication in patients undergoing allogeneic HSCT (Mattee et al., 2004; Sclomchik, 2007). Acute GVHD is caused by donor T cells that recog- nize and react to major histocompatibility complex (MHC) differ- ences between the donor and recipient. It was recently reported that host and/or donor-derived dendritic cells (DCs) are involved in the incidence and persistence of GVHD in a murine model (Duffner et al., 2004; Koyama et al., 2009). Furthermore, it was reported that regulatory DCs protect mice from murine acute GVHD (Sato et al., 2003). DCs play key roles in immune regulation as professional antigen- presenting cells. DCs consist of heterogeneous subsets, including con- ventional DCs and plasmacytoid DCs. There are three stages of differ- entiation: DCs precursors, immature DCs (iDCs), and mature DCs (mDCs) (Banchereau and Steinman, 1998; Banchereau et al., 2000; O'Neill et al., 2004). iDCs are localized in various tissues, and migrate to inflammatory sites in response to chemokines such as CC- chemokine ligand CCL5 through their surface CCR5 expression. At Life Sciences 89 (2011) 946–955 ⁎ Corresponding author at: Department of Radiological Life Sciences, Division of Medical Life Sicences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan. Tel./fax: + 81 17239 5938. E-mail address: ikashi@cc.hirosaki-u.ac.jp (I. Kashiwakura). 0024-3205/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.lfs.2011.10.005 Contents lists available at SciVerse ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie