Immune responses to Epstein-Barr Virus (EBV) encoded Latent Membrane Protein 1 (LMP1) peptides in seropositive donors are dominated by the induction of IL-10 secretion. These IL-10 responses, characteristic of T regulatory 1 (Tr1) cells, were able to inhibit T-cell proliferation and interferon-γ (IFN-γ) section induced by other antigens. Furthermore, this inhibition was specific to the co-presented antigen and persisted after LMP1 peptide had been removed. Thus, it may be possible to exploit such specific induction therapeutically to inhibit pathogenic responses in immune-mediated diseases. The current study was initiated to confirm and extend these findings and then to investigate the ability of LMP1 peptides to inhibit pathogenic responses to Rh autoantigen in AIHA patients <i>in vitro</i>. Inhibitory properties of LMP1 peptides were confirmed, although most such inhibition appeared non-specific and was not associated with IL-10. Inhibition appeared to involve an effect on antigen presenting cells. When autologous red cells or RhD peptides were used as stimulating antigens in patients with AIHA, IL-17 responses were more frequent than IFN-γ secretion. Furthermore, disease activity correlated better with IL-17 responses than TH1 responses. These data therefore suggest that the pathogenesis of AIHA has a substantial Th17 component. Finally, these autoreactive responses could be inhibited by LMP1 peptides.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:509153 |
| Date | January 2009 |
| Creators | Zamzami, Omar M. |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=59565 |
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