Afuwape, Adeyemi O.; (1999) Oral tolerance and sensitisation: Immunoregulation after feeding of ovalbumin and cow's milk. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Oral tolerance (OT) is the antigen specific suppression of systemic immunity with the prior feeding of a protein antigen. Previous studies have employed single protein antigens rather than antigen mixtures as oral tolerogens and the present study was initiated to compare the ability of ovalbumin (OVA) and cow's milk antigen (WP) to induce OT in this model. WP suppressed systemically induced DTH responses but not specific IgG levels, unlike OVA which tolerised both. In an attempt to investigate whether WP could tolerise the more susceptible IgE responses, alum replaced CFA as the adjuvant for systemic immunisations. OVA evoked tolerogenic responses in all parameters whereas WP induced significantly primed DTH and total IgE responses. In addition, in vitro cultures revealed that OVA feeding suppressed antigen specific proliferation and cytokine secretion by mononuclear cells of the draining lymph nodes. WP specific proliferation was not suppressed and cytokines Interleukin (IL) IL-4, IL-10 and IL-12 were up-regulated in cultures from sensitised mice fed WP. Transforming growth factor β (TGF-β) was not detected in any cultures from mice fed either OVA or WP. On examination, only mucosally derived mononuclear cells from OVA fed mice secreted TGF-β and IL-10. This was apparent before and after immunisation. Seven days after immunisation, cytokine patterns for both antigens were comparable to those found in the periphery. Kinetic studies, however, revealed that OVA feeding increased both IL-10 and Interferon-γ (IFN-γ) concentrations. Whilst IL-4 was not detected in cultures derived from tolerant mice, mRNA IL-4 expression was found in almost all mesenteric lymph nodes (MLN). Whole mount in situ hybridisation conducted on Peyer's patches (PP) revealed cytokine expression in T cell dependent areas but not in germinal centres populated by B cells. TGF-β was consistently expressed in Peyer's patches from tolerant mice whereas primed mice possessed PP containing transcripts for IL-12. The data suggests a possible antagonistic relationship between these cytokines in the different immuoregulatory patterns of tolerised and sensitised mice.

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