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Title: Oral tolerance to soluble protein antigens in humans
Author: Boulton-Jones, John Robert
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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In this thesis, a protocol to demonstrate oral tolerance is described. Keyhole limpet haemocyanin (KLH), a neo-antigen, was used to demonstrate low dose tolerance. A control group was immunised with KLH and the subsequent immune response was assessed by delayed type hypersensitivity responses, in vitro lymphocyte proliferation to KLH and anti-KLH IgG and IgA production. Another group of volunteers was pre-fed a course of KLH prior to receiving the same immunisation schedule. The same measures of the immune response used in the control group were assessed and any differences were attributed to oral tolerance. A third group of volunteers was immunised with ovalbumin (OVA) and the immune response was measured. OVA is a common dietary protein and therefore was used to assess oral tolerance to extended courses of feeding. The group fed 50mg of KLH for 10 days demonstrated reduced DTH responses but without significant differences in in vitro lymphocyte proliferation and priming of anti-KLH IgG production. These changes demonstrated that oral tolerance can occur in the T cell compartment in humans after a short course of antigen feeding. In contrast, those volunteers immunised with OVA showed no in vitro lymphocyte proliferation or DTH responses. Anti-OVA IgA and IgA were detectable in low levels prior to immunisation but there was no increase in humoral response after immunisation. These results suggest that oral tolerance is more pronounced to an antigen that has been encountered over prolonged periods. The nature of the tolerance to KLH is not known. It may be the result of the induction of immunoregulatory cells or the induction of clonal anergy. Experiments were designed to test for the presence of immunoregulatory cells induced by feeding KLH, but no positive results were obtained. The mechanisms maintaining tolerance to OVA are likewise unknown. Attempts to demonstrate clonal anergy by reserving tolerance with IL-2 failed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available