Theses and Dissertations at Montana State University (MSU)
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Item Molecular characterization of the primary adhesion mechanisms that direct [gamma/delta] T cells to epithelial-associated tissues(Montana State University - Bozeman, College of Agriculture, 1994) Walcheck, Bruce KennethItem Analysis and characterization of tissue specific accumulation of TCR-defined [gamma delta] T cell subsets in the bovine system(Montana State University - Bozeman, College of Agriculture, 2000) Wilson, EricItem Biochemical and functional analysis of a novel lineage-specific gamma delta T cell surface antigen (GD3.5Ag)(Montana State University - Bozeman, College of Agriculture, 1997) Jones, Ward McAlisterItem Primary and secondary in vitro generation of bovine cytotoxic T lymphocytes(Montana State University - Bozeman, College of Agriculture, 1984) Senta, Kathleen ElizabethItem Vaccine platform for infection or autoimmune diseases using an ETEC fimbrial scaffold(Montana State University - Bozeman, College of Agriculture, 2009) Jun, SangMu; Chairperson, Graduate Committee: David Pascual.The expression of enterotoxigenic Escherichia coli (ETEC) fimbriae (colonization factor antigen I (CFA/I) or K99) on the surface of a Salmonella vaccine vector confers protection against ETEC challenge. Application of such fimbriae as a treatment for the proinflammatory disease, experimental autoimmune encephalomyelitis (EAE), or as a molecular scaffold for heterologous antigen expression by cloning enterohemorrhagic E. coli (EHEC) LPS peptide mimetics into the K99 fimbriae to produce a dual vaccine for ETEC/EHEC was investigated. The expression of CFA/I fimbriae by a Salmonella vaccine vector stimulates a biphasic T helper (Th) cell response and suppresses proinflammatory responses suggesting that CFA/I fimbriae may be protective against proinflammatory diseases. To test this hypothesis, SJL/J mice were vaccinated with Salmonella-CFA/I vaccine 1 or 4 wks prior to induction of EAE induced with encephalitogenic proteolipid protein (PLP) peptide, PLP₁₃₉-₁₅₁. Mice receiving Salmonella-CFA/I vaccine recovered completely from the mild acute clinical disease and showed only mild inflammatory infiltrates in the spinal cord. This protective effect was accompanied by a loss of encephalitogenic IFN-gamma secreting Th1 cells and replaced with increases in IL-4-, IL-10-, and IL-13- producing Th2 cells. These data suggest that Salmonella-CFA/I is an anti-inflammatory vaccine capable of suppressing proinflammatory cells to protect against EAE via immune deviation. To obtain an effective nasal vaccine for ETEC, the fanC gene of ETEC K99 major structural gene was cloned onto the reovirus adhesin, protein sigma1, which has been shown as an M cell targeting molecule. Although FanC/protein sigma1 fusion protein was successfully expressed, this vaccine failed to elicit immune responses against native FanC protein, presumably because of improper protein folding. Using K99 fimbriae as a molecular scaffold, a LPS peptide mimetic for EHEC was cloned into the fanH gene of K99 fimbriae minor structural gene to enable multiple antigenic peptide expression, resulting in an ETEC/EHEC dual vaccine. Insertion of peptide mimetic into fanH gene had no adverse effect on the formation of polymerized K99 fimbriae. However, various oral immunization regimens failed to induce the protective secretory IgA responses against the LPS mimetic peptide, although serum IgG antibodies were induced.Item Select Procyanidins induce gammadelta T cell activation and proliferation(Montana State University - Bozeman, College of Agriculture, 2008) Holderness, Jeffrey Scott; Chairperson, Graduate Committee: Mark Jutila.Many pharmaceutical drugs in use today were originally identified in plants from traditional medicine. However, there remain many plants in traditional medicine that produce confusing immune responses and are therefore unlikely candidates for pharmaceutical drugs. The effects of some of the traditional medicines that induce these confusing immune responses may now be explained by recent advances in the characterization of our immune system, namely in our understanding of the unique functions of the gammadelta T cell. These gammadelta T cell functions include tissue repair and homeostasis, cancer infiltration and clearance, pathogen detection and cytokine response, and antigen presentation. Although there are currently therapies being studied to increase the effector function of gammadelta T cells, these techniques are only active on a limited population of gammadelta T cells, the human Vdelta2 subset. Although these cells are potent effectors against pathogens and some cancers, Vdelta2 T cells demonstrate a restricted tissue distribution and limited effector function in other gammadelta T cell host defense responses. As such, we screened compound libraries and traditional medicines for agonists with activity encompassing alternative gammadelta T cell subsets. Tannins derived from select plant species are able to fulfill this role as demonstrated by the activation and expansion of gammadelta T cell subsets not responsive to current gammadelta T cell expansion therapies. The ability of tannins to expand these gammadelta T cell populations will potentially increase the therapeutic range of gammadelta T cells and may be used as treatments for wound healing as well as in the clearance of solid tumor cancers.Item Comprehensive transcriptional profiling of gamma delta T cells(Montana State University - Bozeman, College of Agriculture, 2005) Graff, Jill Christin; Chairperson, Graduate Committee: Mark Jutila.gamma delta T cells have been conserved since the adaptive immune system arose, yet their importance is still unclear. In an attempt to compensate for the lack of a broad knowledge-base of gamma delta T cells across species, global analyses of gamma delta T cell transcriptomes have been performed using serial analysis of gene expression (SAGE). Twelve new SAGE libraries were generated from the following bovine lymphocyte populations: magnetic bead-sorted blood gamma delta T cells, spleen gamma delta T cells and enriched alpha beta T cells from a single calf, both rested and ConA/IL-2 stimulated, and flow cytometry-sorted blood gamma delta and alpha beta T cells each either rested, ConA/IL-2, or PMA/ionomycin stimulated. These databases were analyzed using new web-based bioinformatic tools, which allow the user to rapidly compare gene expression patterns within these and other SAGE and standard EST libraries generated from different cell types and different species. These analyses revealed striking differences between blood and spleen gamma delta T cells and how these cells respond to various mitogenic stimulation. These analyses also confirm previous studies that suggest that global gene expression in gamma delta and alpha beta T cells is quite similar; however, a five-fold increase in gamma delta T cell-specific transcripts could be induced by ConA/IL-2 stimulation of spleen cells. Even greater differences were seen between the two lymphocyte populations isolated from blood, regardless of activation state. These new public databases provide additional resources for the annotation/analysis of global gene expression in gamma delta T cells, which will facilitate studies of the biology of this enigmatic lymphoid cell.