It is widely believed that generation of mature dendritic cells (DCs) with full T cell stimulatory capacity from human monocytes in vitro requires 5–7 days of differentiation with GM-CSF and IL-4, followed by 2–3 days of activation. Here, we report a new strategy for differentiation and maturation of monocyte-derived DCs within only 48 h of in vitro culture. Monocytes acquire immature DC characteristics by day 2 of culture with GM-CSF and IL-4; they down-regulate CD14, increase dextran uptake, and respond to the inflammatory chemokine macrophage inflammatory protein-1α. To accelerate DC development and maturation, monocytes were incubated for 24 h with GM-CSF and IL-4, followed by activation with proinflammatory mediators for another 24 h (FastDC). FastDC expressed mature DC surface markers as well as chemokine receptor 7 and secreted IL-12 (p70) upon CD40 ligation in the presence of IFN-γ. The increase in intracellular calcium in response to 6Ckine showed that chemokine receptor 7 expression was functional. When FastDC were compared with mature monocyte-derived DCs generated by a standard 7-day protocol, they were equally potent in inducing Ag-specific T cell proliferation and IFN-γ production as well as in priming autologous naive T cells using tetanus toxoid as a model Ag. These findings indicate that FastDC are as effective as monocyte-derived DCs in stimulating primary, Ag-specific, Th 1-type immune responses. Generation of FastDC not only reduces labor, cost, and time required for in vitro DC development, but may also represent a model more closely resembling DC differentiation from monocytes in vivo.

The known sequelae of sexual abuse include acute and chronic injury. The purpose of this study was to evaluate the association of overactive bladder symptoms (OABs) with a history of physical or sexual abuse. Two hundred and forty-three women who attended the gynaecological out-patient clinic or the urogynaecological clinic were recruited for our study. Based on their clinical examination, they were assigned to three groups of patients with either OAB or with stress urinary incontinence (SUI) without concomitant urgency symptoms (SUI), or without history of incontinence (control group). Afterwards, they completed an anonymous questionnaire about bladder function and physical/sexual violence. Significantly more women (30.6%, 26/85) with OAB had previously been physically or sexually abused than women with SUI (17.8%, 18/101) and of the control group (17.5%, 10/57). Our study showed that significantly more women with OAB report physical and sexual abuse than subjects with stress incontinence or no urinary complaints. Women with stress incontinence had the same rate of self-reported physical/sexual abuse as continent controls.

SUMMARYDendritic cells (DC) can be derived from monocytes in vitro by culture with granulocyte± macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). It is unknown whether this regimen re¯ects DC differentiation from blood precursors under physiological conditions. Induction of DC development from monocytes by interferon-a (IFN-a) may occur in vivo during infection or in¯ammation and thus may represent a more physiological approach to DC differentiation in vitro. Here, we show that incubation of GM-CSF-cultured monocytes with IFN-a does not induce DC differentiation: cells maintain their original phenotype and cytokine secretion pattern. Even after stimulation with pro-in¯ammatory or T-cell-derived activation signals, IFN-a-treated monocytes do not develop DC characteristics. Addition of IL-4 during stimulation of IFN-a-treated monocytes results in the rapid development of DC-like cells expressing co-stimulatory molecules, CD83 and chemokine receptor CCR7, indicating that some degree of developmental plasticity is preserved. However, DC pre-activated with IFN-a are less effective in inducing allogeneic or antigen-speci®c autologous T-cell proliferation, produce less IL-12 and express lower levels of CCR7 compared to DC generated by culture with GM-CSF and IL-4. Incubating GM-CSF-cultured monocytes simultaneously with IFN-a and IL-4 does not affect phenotypic maturation of DC, but reduces IL-12 production upon pro-in¯ammatory activation. We conclude that: (1) IFN-a fails to induce DC differentiation and thus cannot replace IL-4 in generating DC from monocytes in vitro; and (2) the presence of IFN-a prior to or during differentiation of DC from monocyte precursors alters their response to maturation stimuli and may affect their capacity to stimulate T helper type 1 immune responses in vivo.

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