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Prepublished online as a Blood First Edition Paper on July 12, 2002; DOI 10.1182/blood-2002-01-0231.
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Blood, 1 November 2002, Vol. 100, No. 9, pp. 3287-3294
IMMUNOBIOLOGY
Sézary syndrome patients demonstrate a defect in dendritic
cell populations: effects of CD40 ligand and treatment with
GM-CSF on dendritic cell numbers and the production of
cytokines
Maria Wysocka,
Mohamed H. Zaki,
Lars E. French,
Jihed Chehimi,
Michael Shapiro,
Suzanne E. Everetts,
Karen S. McGinnis,
Luis Montaner, and
Alain H. Rook
From the Department of Dermatology, University of
Pennsylvania, Philadelphia; the Department of Dermatology, Geneva
University Hospital, Switzerland; and The Wistar Institute,
Philadelphia, PA.
Sézary syndrome (SzS) is an advanced form of cutaneous T-cell
lymphoma associated with involvement of the peripheral blood by
malignant T cells. The disease is defined by impaired cell-mediated immunity and the production of interferon- (IFN-) and
interleukin-2 (IL-2), possibly as a result of deficient IL-12
production. To understand the mechanism of this impairment, we examined
the composition and function of dendritic cells and monocytes in the
blood of SzS patients with different levels of peripheral blood tumor
burden. Consistent with our previous observations, numbers of monocytes in SzS patients were comparable to numbers observed in healthy donors.
In contrast, decreased IL-12 production correlated with a decrease in
the numbers of CD11c+ dendritic cells, which was
particularly profound among patients with medium (20%-50% circulating
malignant T cells) and high (more than 50% circulating malignant T
cells) tumor burden. Furthermore, CD123+ dendritic cells,
major producers of IFN- , were significantly diminished in SzS
patients, regardless of the level of tumor burden. Granulocyte
macrophage-colony-stimulating factor-treated patients experienced an increase in the number of dendritic cells but not in
IFN- or IL-12 production. However, in vitro stimulation of peripheral blood mononuclear cells from SzS patients with rCD40L and
IFN- significantly increased the production of IL-12. Thus, our
results demonstrate a profound defect in circulating dendritic cells in
SzS patients that may contribute to the pathogenesis of the cytokine
disorders and to the depressed cellular immunity. Importantly, the
ability of rCD40L to potently induce IL-12 production from monocytes
and residual dendritic cells of SzS patients could potentially serve as
an immune-restorative therapeutic agent.
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