Upregulation of the Chemokine Receptor CCR5 on CD16+ Myeloid Blood Dendritic Cells in Allogeneic Hemopoietic Cell Transplant Patients Predicts for Acute Graft Versus Host Disease

Dendritic cells (DC) are centrally involved in the development of acute graft-versus-host disease (GvHD) following allogeneic hemopoietic cell transplantation (alloHCT). We previously showed that the activation status, as assessed by CMRF-44 antigen expression, of CD11c+ myeloid blood DC is highly associated with the onset and severity of acute GvHD (Transplantation. 2007;83:839–846). We also reported a positive correlation between acute GvHD and the expression of the chemokine receptor CCR5 on CD11c+ myeloid DC (Blood. 2009;114 Suppl.:2251). Given the phenotypic and functional heterogeneity of the CD11c+ DC population, we investigated CCR5 expression on the CD11c+ DC subsets and then monitored the informative CD11c+ CD16+ DC subset expression of CCR5 in the peripheral blood of 42 patients post alloHCT, and correlated the findings with GvHD.

Peripheral blood was collected twice weekly up to Day 100 post transplant from 42 alloHCT patients. The expression of CCR5 receptor on CD11c+ and CD11c- DC subsets was evaluated using multiparameter flow cytometry.

Only the CD11c+ CD16+ DC subset lacked CCR5 and induced it upon alloactivation. Seventeen of 42 patients developed acute GvHD (5 grade I, 12 grades II-IV). The percentage of CD11c+ CD16+ DC expressing CCR5 correlated with the development of acute GvHD grades II-IV. The maximum CCR5 expression detected on CD11c+ CD16+ DC in patients prior to developing grades II-IV GvHD (mean 22.7 ± 4.3%, n=12) was higher than in those with grades 0-I GvHD (11.4 ± 1.7%, n=30) (p=0.0285). CCR5 levels >20% on CD16+ myeloid DC predicted grades II-IV GvHD with a sensitivity of 66.7% and specificity of 86.7%. Levels of expression of CCR5 on the CD11c+ CD16- DC and CD123+ plasmacytoid DC were not predictive of GvHD.

Expression of CCR5 on circulating CD11c+ CD16+ myeloid DC post alloHCT correlated with the development of moderate to severe GvHD. This observation may reflect DC activation or altered DC homing during the alloimmune response. Detection of increased CCR5+ CD11c+ CD16+ DC may allow pre-emptive therapeutic intervention prior to the clinical diagnosis of GvHD.

No relevant conflicts of interest to declare.