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Title: Immunoregulatory T cell populations during nematode infections
Author: Finney, Constance Ann Marjory
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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We have found that a primary infection with the gastrointestinal nematode Heligmosomoides polygyrus elicits a potent CD4+CD25+ regulatory T cell (Treg) population within a generalised TH2 environment. This indicates that long-lived nematode parasites may exploit the host regulatory network to suppress protective immunity. We followed the expansion of CD4+CD25+ Treg cells within the mesenteric lymph nodes (MLN) and spleen over 70 days of infection. Over the time course, increased levels of IL-4, IL-5, IL-9, IL-13 and IL-10 were detected in both these sites by in vitro recall response to parasite antigen. In infected animals, Treg markers, such as surface bound TGF-β1 and CD103 were upregulated on CD4+CD25+ MLN cells. Surprisingly, however, Foxp3, a transcription factor necessary for Treg development and function, was not upregulated on CD4+CD25 + in infected animals. Additionally, we have demonstrated that this regulatory population has potent in vitro and in vivo suppressive activity. CD4+CD25+MLN cells from infected animals (day 28) can suppress mitogen-induced proliferation by both naïve and infected CD4+CD25- cells, whilst naïve CD4+CD25+MLN cells can only suppress naïve CD4+CD25- cells. Moreover, in a model of allergic airway inflammation, we observed that allergic inflammation was decreased in both infected animals and those cured of infection before airway challenge. Thus, infection is required to induce but not maintain this regulatory function. Finally, we found that concomitant H. polygyrus infection led to reduced expulsion of the related strongylid nematode Nippostrongylus brasiliensis in co-infected hosts. Regulatory markers, CD103 and TGF-β1, as well as TH2 cytokines were elevated in co-infected animals as compared to those with a single N. brasiliensis infection. However, re-infection with H. polygyrus of both cured and infected animals led to significant decreases in worm burden, so although the regulatory network generated by this parasite can increase survival of other nematodes, it does not suppress immune responses to itself upon re-infection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available