V Bachy

Publications (2)6.33 Total impact

• Article: Altered dendritic cell function in normal pregnancy.

  V Bachy, D J Williams, M A A Ibrahim
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  ABSTRACT: In pregnancy, maternal immunity is skewed to favour maintenance of gestation and immune tolerance of a semi-allogeneic fetus. Dendritic cells are thought to play a crucial role in mediating the balance between immunity and tolerance, and determining the type of T helper cell response. We postulated that myeloid dendritic cells would be modified in pregnancy to favour type 2 T helper cell responses. We show that the proportion of circulating myeloid dendritic cells expressing CD86 and staining for HLA-DR were significantly lower in the third trimester of pregnancy compared with non-pregnant women. As pregnancy progressed through the third trimester to term, CD86 expression increased. Furthermore, monocytes from pregnant women differentiated into less phenotypically mature dendritic cells which expressed lower levels of CD80, CD86 and HLA-DR molecules compared with non-pregnant women. In response to inflammatory stimuli, monocyte-derived dendritic cells, from pregnant women up-regulated CD86 more than CD80, and secreted less IL-12p70 but more IL-10, compared with monocyte-derived dendritic cells from non-pregnant controls. Our results demonstrate that, in pregnancy, the dendritic cell system is modified to favour type 2 T helper cell responses.
  Journal of Reproductive Immunology 07/2008; 78(1):11-21. · 2.97 Impact Factor
• Article: Regulation of dendritic cell interleukin-12 secretion by tumour cell necrosis.

  H Kandil, V Bachy, D J Williams, R Helmi, F M Gotch, M A A Ibrahim
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  ABSTRACT: Dendritic cells (DCs) play a key role in the induction and regulation of antigen-specific immunity. Studies have shown that, similar to infection, cellular necrosis can stimulate DC maturation. However, the ability of necrotic cell death to modulate DC cytokine secretion has yet to be explored. We investigated the regulation of interleukin (IL)-12 secretion by human DCs in response to tumour cell necrosis in an in vitro culture model. Two human tumour cell lines (K562 and JAr) were induced to undergo necrosis using heat injury and repeated cycles of freezing and thawing. Both types of tumour cells tested in this study, when injured, induced secretion of monomeric IL-12p40 by monocyte-derived DCs. Furthermore, priming DCs with necrotic cells augmented IL-12p70 secretion significantly in conjunction with CD40 cross-linking. This was physiologically relevant because cell death-pulsed DCs were more potent than non-pulsed DCs at stimulating T cells to proliferate and secrete interferon (IFN)-gamma. The Toll-like receptor 4 (TLR4) played a role in mediating the DC response to heat-killed, but not freeze/thaw-killed necrotic cells. For both methods of injury, proteins contributed to the effect of necrosis on dendritic cells, whereas DNA was involved in the effect of freeze/thawed cells only. These findings indicate that necrotic tumour cell death is not sufficient to induce bioactive IL-12p70, the Th1 promoting cytokine, but acts to augment its secretion via the CD40/CD40L pathway. The results also highlight that the mode of cell death may determine the mechanism of dendritic cell stimulation.
  Clinical & Experimental Immunology 05/2005; 140(1):54-64. · 3.36 Impact Factor