| dc.contributor.author | Liwski, Robert Stefan. | en_US |
| dc.date.accessioned | 2014-10-21T12:33:51Z | |
| dc.date.available | 1999 | |
| dc.date.issued | 1999 | en_US |
| dc.identifier.other | AAINQ49276 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55657 | |
| dc.description | Previous research from our laboratory demonstrated that infection of rats with the intestinal nematode Nippostrongylus brasiliensis (Nb), which induces strong Th2 responses, significantly prolongs the survival of fully allogeneic vascularized kidney grafts. The focus of this thesis is to investigate the manner in which Nb infection affects allo-reactivity to provide information to support or refute a hypothesis that these observed effects of A infection relate to type 2 dominant response. The importance of T cells in graft rejection focussed the research on the effects of Nb infection on T cell activation, T cell proliferation and differentiation, all aspects of T cell function critical to allo-reactivity. | en_US |
| dc.description | It was found that T cells from mice infected with Nb prior to allo-immunization exhibit significantly reduced allo-specific CTL activity. In contrast, allo-specific proliferation in the MLR was not reduced by Nb, ruling out immunosuppression. Analysis of MLR culture supernatants by ELISA showed that Nb infection induced the production of type 2 cytokines and significantly inhibited production of type 1 cytokines. Further, staining of spleen T cells for CD8 and cytoplasmic IL-4 showed that Nb infection results in an 8-fold increase in the number of CD8 +, IL-4-producing Tc2 cells. These results are consistent with a hypothesis that, Nb mediates prolongation of allograft survival through induction of type 2 immunity,, including the development of regulatory Tc2 cells. | en_US |
| dc.description | The shift in the development of type I allo-specific responses towards type 2 immunity that occurred in the presence of Nb infection suggested that the nematode has immuno-modulatory effects on T cell activation. It was found that spleen cells from Nb-infected mice exhibited dramatically increased proliferation in response to Con A and anti-CD3. This hyper- proliferation could be transferred, in vitro, to naive splenocytes by co-culture with mitomycin C-treated cells from Nb-infected animals. The transfer was mediated by non-T accessory cells, and supernatants derived from Con A-activated non-T cells, suggesting the involvement of a soluble factor. The accessory cells secreted high levels of IL-6, and anti-IL-6 treatment abrogated the supernatant-induced hyper-proliferation, thus confirming that IL-6 was mediating the effect. Further, spleen cells from Nb -infected mice were more resistant to activation induced cell death (AICD) following mitogenic stimulation. Reduced AICD was also transferable and IL- 6-dependent. Thus, the hyper-proliferation was, in large part, due to enhanced activated T cell survival. | en_US |
| dc.description | These studies suggest that nematodes can induce powerful polyclonal activation of type 2 immunity by alteration of accessory cell function. It is postulated that one mechanism by which this type 2 switch might occur is by the inhibition of AICD in activated T cells allowing progression through sufficient cycling events to promote Th2/Tc2 phenotypes. The results of these studies have significant implications with respect to the regulation of immune responses to other antigens in countries where nematode infection is endemic. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 1999. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Biology, Cell. | en_US |
| dc.subject | Health Sciences, Immunology. | en_US |
| dc.title | Modulation of T cell-mediated responses by Nippostrongylus brasiliensis. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
