The purpose of this study was to clarify the relationship between the cellular and humoral immune components in the pathogenesis of vitiligo vulgaris. By using cytokines as indicators of peripheral mononuclear cell (MNC) function, we compared the effects of phytohemagglutinin (PHA) and purified IgG on MNCs derived from patients suffering from active vitiligo with those from normal controls. The results revealed (i) a significant increase in spontaneous production of IL-6 and IL-8 in patients; (ii) PHA, purified IgG from patients (IgG-anti-MC), or IgG from normal controls (N-IgG) induced a significant increase in IL-6 but diminished GM-CSF, TNF-alpha, and IFN-gamma release in patients; and (iii) IgG-anti-MC brought about a significantly higher stimulatory effect on IL-1beta and IFN-gamma production than N-IgG in normal controls. Immunologically, IL-6 can enhance melanocyte ICAM-1 expression, which may increase leukocyte-melanocyte attachment and cause melanocyte damage in vitiligo. A decrease in GM-CSF (an intrinsic growth factor for melanocyte) production may retard recovery from vitiligo by checking the proliferation of surviving melanocytes. A significant decrease in TNF-alpha and IFN-gamma production may partially explain the reduced inflammatory reaction in vitiliginous lesions. That IgG-anti-MC stimulates an increase in IL-1beta and IFN-gamma production in controls suggests that IgG-anti-MC may play a role in melanocyte destruction mediated by monocytes.

The binding of a T cell to an Ag-laden dendritic cell (DC) is a critical step of the acquired immune response. Herein, we address whether a DC-produced chemokine can induce the arrest of T cells on DC under dynamic flow conditions. Ag-primed T cells and a T cell line were observed to rapidly (∼0.5 s) bind to immobilized DC at low shear stress (0.1–0.2 dynes/cm2) in a pertussis toxin-sensitive fashion. Quantitatively, Ag-primed T cells displayed 2- to 3-fold enhanced binding to DC compared with unprimed T cells (p < 0.01). In contrast to naive T cells, primed T cell arrest was largely inhibited by pertussis toxin, neutralization of the CC chemokine, macrophage-derived chemokine (CCL22), or by desensitization of the CCL22 receptor, CCR4. Our results demonstrate that DC-derived CCL22 induces rapid binding of activated T cells under dynamic conditions and that Ag-primed and naive T cells fundamentally differ with respect to chemokine-dependent binding to DC.

No abstract

No abstract

To address whether matrix metalloproteinase (MMP)-2 expression by mesenchymal fibroblasts may be differentially modulated by interactions with normal or malignant epidermal cells, we set up a fibroblast co-culture model separately with keratinocytes, basal cell carcinoma cells and melanoma cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) and gelatin zymography were used to detect and quantify the expression of MMP-2 by these different kinds of cells. In independent cultures, MMP-2 was highly expressed by fibroblasts and melanoma cells constitutively, but barely expressed by keratinocytes and basal cell carcinoma (BCC) cells. MMP-2 expression by fibroblasts was downregulated in co-cultures with keratinocytes or BCC cells, but not with melanoma cells. These results indicate that epidermal-mesenchymal interactions are important modulators for MMP-2 expression by cutaneous cells and suggest a host-defense mechanism against the tumor progression of BCC.