LETTER TO THE EDITOR Does Nitric Oxide Generated by Dendritic Cells Contribute to the Low Incidence of GVHD after Cord Blood Transplantation

Cord Blood Transplantation (CBT) has a significantly lower incidence of graft-versus-host disease (GVHD) compared to marrow or peripheral blood transplantation (1). There are largely unknown T-cell silencing factors involving in the less severe GVHD after CBT. Sorg et al. highlighted the lower functional capacity of the Cord Blood Dendritic Cells (CBDCs) (2). The available evidence shows that there are a multitude of differences between CBDCs and PBDCs: CBDCs are in general functionally immature with low expression of costimulatory molecules, deficient in interleukin-12 (IL-12) production, less effective in stimulating T-cell proliferation, and therefore favoring immune tolerance (3). In this study, we have approached the low risk of GVHD in CBT from a new angle by focusing on DC-derived Nitric Oxide (NO) which has recently been shown to inhibit T cell proliferation and induce T cell apoptosis (4). We designed experiments to determine whether an increase in NO synthesis in CBDCs plays a protective role in severe GVHD and evaluated NO production in Mixed Leukocyte Reaction (MLR) using pure populations of CBDCs and PBDCs. A total of 14 samples of fresh CBDCs and PBDCs were isolated as lineage-negative cells according to a slightly modified protocol described previously (5). Using a cocktail of PE conjugated anti-lineage markers (CD3, CD19, CD34, CD16, CD56, CD14, CD11b, and CD66b), FITC conjugated anti-HLA-DR monoclonal antibodies, and flow cytometric analysis, the frequency of Lin- HLA-DR cells (DCs) was determined to be 58.5 ± 4.5 % and 45 ± 12 % of enriched cells from PB and CB, respectively.