The adult stage of the parasitic nematode <i>Brugia malayi</i> can live in the host lymphatics for many years and must have an extremely effective immuno-suppressive mechanism that prevents rejection. We have discovered that this parasite can induce alternatively activated IL-4 dependent macrophages that can block proliferation of other cells via a receptor-mediated mechanism. The proliferative block is reversible and is not a result of apoptosis. Furthermore, these suppressive cells can reduce the proliferation of a wide range of human cancer cell lines. These data demonstrates that <i>B. malayi</i> can lead to the activation of a novel mechanism of proliferative suppression, via IL-4 dependent macrophages. These macrophages may have important roles in altering host immune responses during parasitic infection and may even have the potential to reduce tumour cell growth. Another feature of <i>B. malayi </i>infection is a bias towards a type 2 immune response. To investigate the role that the <i>B. malayi </i>recruited antigen presenting cells have on naive T cells, the suppressive macrophages recruited by <i>B. malayi </i>was used to stimulate naive T cells from TCR transgenic mice. Although the naive T cells were inhibited by parasite-induced macrophages during primary stimulation, they proliferated normally upon secondary stimulation and were not rendered anergic. However, naive T cells primed by suppressive macrophages differentiated into IL-4 producing Th2 cells upon secondary stimulation instead of IFN-g producing Th1 cells, as has been previously described. Th2 differentiation was associated with the inhibition of (or failure or stimulate) IFN-g production during primary stimulation. Interestingly, blocking antibodies against TGF-b (but not IL-10) restored the differentiation of IFN-g producing Th1 cells. These data indicate that T cells exposed to parasite induced alternatively activated macrophages are driven towards Th2 differentiation. This may be an important factor in the Th2 bias that accompanies helminth infection.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:654011 |
| Date | January 2000 |
| Creators | Loke, P. |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/12460 |
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