Alterations in Chemokine Receptor CCR5 Expression on Blood Dendritic Cells Correlate With Acute Graft-Versus-Host Disease

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Abstract

Background

Dendritic cells (DC) are important in the development of acute graft-versus-host disease (GVHD) after allogeneic hemopoietic cell transplantation (alloHCT). The trafficking of immature DC from blood to GVHD target organs is likely to be regulated by chemokine receptors.

Methods

We performed flow cytometry to document the expression of chemokine receptors on circulating DC and correlated the findings after alloHCT with occurrence of acute GVHD.

Results

In normal individuals, plasmacytoid DC (pDC) expressed high levels of CCR5, whereas the major CD16+ myeloid DC subpopulation lacked CCR5. However, its expression on CD16+ cells was induced by culture in allogeneic mixed lymphocyte reaction supernatant, an effect largely mediated by interferon-γ. CCR5 was expressed on a significant proportion of CD16+ DC in 42 alloHCT patients, whereas it was down-regulated on pDC. The maximum percentage of CCR5+CD16+ DC, at any time after transplantation, correlated with acute GVHD, whereas the minimum CCR5+ on pDC showed a similar correlation. Before developing signs of GVHD, the maximum percentage CCR5+CD16+ DC was higher in patients with GVHD grades II to IV than in GVHD grades 0 and I, whereas the minimum percentage CCR5 on pDC was lower in GVHD grades II to IV than in GVHD grades 0 and I. CCR5 levels more than 20.5% on CD16+ myeloid DC and less than 22.6% on CD123+ pDC correlated with subsequent GVHD grades II to IV with high sensitivities and specificities.

Conclusions

These observations may reflect DC activation and altered homing during the alloimmune response and could allow early diagnosis and therapeutic intervention before the clinical diagnosis of GVHD.

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