Increased donor CD86+CD14+ cells in the bone marrow and peripheral blood of patients with chronic graft-versus-host disease

Transplantation. 2008 Jun 27;85(12):1826-32. doi: 10.1097/TP.0b013e3181788a84.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / pharmacology
  • Antigen-Presenting Cells / immunology*
  • B7-2 Antigen / metabolism*
  • Bone Marrow / immunology*
  • Case-Control Studies
  • Cell Count
  • Chronic Disease
  • Female
  • Graft vs Host Disease / immunology*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology*
  • Lipopolysaccharide Receptors / metabolism*
  • Male
  • Middle Aged
  • Prednisone / pharmacology
  • Retrospective Studies
  • Tissue Donors

Substances

  • Anti-Inflammatory Agents
  • B7-2 Antigen
  • Lipopolysaccharide Receptors
  • Prednisone