期刊
BLOOD
卷 100, 期 9, 页码 3287-3294出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2002-01-0231
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资金
- NCI NIH HHS [CA 10815, CA 20833] Funding Source: Medline
Sezary 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-gamma (IFN-gamma) 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 thin 50% circulating malignant T cells) tumor burden. Furthermore, CD123(+) dendritic cells, major producers of IFN-alpha, 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-alpha or IL-12 production. However, in vitro stimulation of peripheral blood mononuclear cells from SzS patients with rCD40L and IFN-gamma 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. (C) 2002 by The American Society of Hematology.
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