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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-01-0068.
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Blood, 1 August 2002, Vol. 100, No. 3, pp. 941-947
IMMUNOBIOLOGY
Immunologic mechanisms of extracorporeal photochemotherapy in
chronic graft-versus-host disease
Gullu Gorgun,
Kenneth B. Miller, and
Francine M. Foss
From the Departments of Hematology Oncology and
Experimental Therapeutics, Tufts New England Medical Center, Boston,
MA.
Extracorporeal photochemotherapy (ECP) has been shown to be an
effective therapy for patients with acute and chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation, but
its biologic 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+ natural killer cells and a decrease
in the number of CD80+ and CD123+ circulating
dendritic cells (DCs). To further elucidate the effects of ECP on
activated lymphocyte subpopulations and the interaction between
effector lymphocytes and antigen-presenting DCs, we isolated and
characterized DC populations from patients with chronic GVHD undergoing
ECP therapy. Antigen-presenting activity of DCs was 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  .002) after a 2-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 before the initiation of ECP. Nine of
10 patients demonstrated a shift from DC1 to DC2 and as a concordant
shift from a predominantly Th1 (interleukin-2 [IL-2], interferon- )
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 allo-targeted effector T cells and
antigen-presenting DCs.
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