Increased Donor CD86+CD14+ Cells in the Bone Marrow and Peripheral Blood of Patients With Chronic Graft-Versus-Host Disease

BACKGROUND: Based on experimental models, chronic graft-versus-host disease (cGVHD) may depend on activated donor antigen-presenting cells presenting host antigens to donor T cells. METHODS: Peripheral blood (PB) and marrow samples from 24 patients with cGVHD and 17 patients without GVHD after an allogeneic hematopoietic stem-cell transplant were analyzed by flow cytometry. The absolute number of myeloid dendritic cells (mDC) (BDCA1+CD19-), plasmacytoid DC (pDC) (BDCA2+CD123+) and monocytes (CD45+CD14+), and mean fluorescence intensity of costimulatory molecules and chemokine receptors were assessed in each antigen-presenting cell population. RESULTS: Patients with cGVHD showed increased numbers of marrow monocytes when compared with patients without cGVHD (P=0.006). Moreover, monocytes of cGVHD patients had greater CD86 mean fluorescence intensity in marrow (P=0.02) and PB (P=0.04). Treatment with prednisone resulted in decreased CD86 expression in marrow (P=0.02) and PB (P=0.04) monocytes. The number and phenotype of mDC and pDC were similar in patients with or without cGVHD. Full-donor chimerism was detected in the PB of all patients, and in purified CD14+ monocytes from three cGVHD patients. CONCLUSION: Our results show an increased activation of donor-derived marrow and blood monocytes in patients with cGVHD, possibly suggesting the need to target monocytes in the treatment of cGVHD.