Lymphatic filariasis is a long term chronic infection characterised by a Th2 dominated immune response and suppressed Ag-specific proliferation. This immunological hyporesponsiveness is most profound amongst individuals with circulating microfilariae (mf) suggesting an important role for mf in generating proliferative suppression. The use of single life cycle stage infections in murine models of filariasis has facilitated the study of stage specific mechanisms of immunomodulation. Intravenous infection of BALB/c mice with <i>B. pahangi</i> mf or L3 (the third stage larvae) leads to development of differentially polarised immune responses. At 12 d.p.i. splenocytes from L3 infected animals produce Ag-specific IL-4, IL-5 and IL-10 and show strong Ag-driven proliferative responses. In contrast splenocytes from mf-infected animals show a cytokine profile dominated by IFN-gamma and suppression of Ag-specific proliferation. After 96 hrs of Ag-stimulated culture splenocytes from mf-infected animals proliferate at levels below background indicating that an active form of suppression is operable <i>in vitro</i>. A lack of IL-2 does not account for the defective proliferative response as addition of recombinant IL-2 failed to restore Ag-specific proliferation. Splenocytes from mf-infected animals produce high levels of NO in Ag-stimulated culture which correlates inversely with their proliferative responses. No such accumulation of nitrite is seen in cultures of cells from L3 infected animals. The proliferative defect is dependent upon inducible nitric oxide synthase (iNOS) activity as inhibition of iNOS activity with either L-NMMA or AMG restored Ag-specific proliferation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:341741 |
| Date | January 2001 |
| Creators | O'Connor, Richard Anthony |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/6488/ |
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