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.


CONCLUSIONS
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.
Arpinati
Mario
M
Institute of Hematology and Medical Oncology "L.&A.Seragnoli", University of Bologna, Bologna, Italy. arpinati@med.unibo.it
Chirumbolo
Gabriella
G
Marzocchi
Giulia
G
Baccarani
Michele
M
Rondelli
Damiano
D
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D051940:B7-2 Antigen / Q000378:metabolism*; D001853:Bone Marrow / Q000276:immunology*; D016022:Case-Control Studies; D002452:Cell Count; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000494:pharmacology; D012189:Retrospective Studies; D014019:Tissue Donors
D000893:Anti-Inflammatory Agents; D051940:B7-2 Antigen; D018950:Lipopolysaccharide Receptors; D011241:Prednisone