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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-01-0068.
Submitted January 10, 2002
Accepted March 25, 2002
Immunologic mechanisms of extracorporeal photochemotherapy (ECP) in chronic graft-versus host disease
Gullu Gorgun, Kenneth B Miller, and Francine M Foss*
Hematology Oncology and Experimental Therapeutics, Tufts New England Medical Center, Boston, MA, USA
* Corresponding author; email: ffoss{at}lifespan.org.
Extracorporeal photochemotherapy (ECP) has been shown to be an effective therapy for patients with acute and chronic graft-vs-host disease (GVHD) following allogeneic bone marrow transplantation, but its biological mechanism is not understood. We reported that clinical response to ECP was associated not only with normalization of skewed CD4/CD8 ratios, but also with an increase in CD3-/CD56+ NK cells and decrease in the number of CD80+ and CD123+ circulating dendritic cells (DC). To further elucidate the effects of ECP on activated lymphocyte subpopulations and interaction between effector lymphocytes and antigen-presenting dendritic cells, we isolated and characterized DC populations from patients with cGVHD undergoing ECP therapy. Antigen presenting activity of DC, measured as proliferation of antigen-stimulated autologous and allogeneic T cells by mixed lymphocyte reaction (MLR). In MLR assays the proliferation of T cells was decreased in all 10 patients by a mean of 84% (range 75-95%, P 0.002) after a two day cycle of ECP and longitudinally over the 12 month course of therapy. Immunophenotypic analysis of DC populations revealed a preponderance of DC1 monocytic dendritic cells in all patients prior to initiation of ECP. Nine of 10 patients demonstrated a shift from DC1 to DC2, as well as a concordant shift from a predominantly Th1 (IL-2, IFN ) to Th2 (IL-4, IL-10) cytokine profile after ECP, and 8 of 10 had a clinical response to ECP. Our results suggest that ECP alters alloreactivity by affecting both allo-targeted effector T-cells as well as antigen presenting dendritic cells.
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