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Full-Text Articles in Immunology and Infectious Disease

Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain Oct 2018

Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain

Electronic Thesis and Dissertation Repository

Germinal center (GC) responses are responsible for the protection provided by immunizations but can also drive autoimmunity. B and T cells collaborate in the GC to target the same antigen (Ag) to inform B cell differentiation; however, the properties of Ags differ substantially in autoimmunity and foreign-Ag driven immunity. Currently, it is not well understood how properties of the Ag itself influence the initiation or progression of GC responses, limiting our ability to develop effective vaccinations and predict the progression of autoimmune responses. The purpose of this thesis is to assess how GC responses initiate and progress when immunizing with …


Cd4 T Cell Interaction With Intestinal Microbes Under Homeostasis And Inflammation, Jiani Chai Aug 2018

Cd4 T Cell Interaction With Intestinal Microbes Under Homeostasis And Inflammation, Jiani Chai

Arts & Sciences Electronic Theses and Dissertations

Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (Treg) cells responses. However, the bacteria that induce effector T (Teff) cells during inflammation are unclear. Here, we addressed this by analyzing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both Treg responses during homeostasis and Teff responses during colitis, as suggested by an increased overlap between the Teff/Treg TCR repertoires with colitis. In fact, 4/6 Treg TCRs tested recognized mucosal-associated Helicobacter species in vitro and in vivo. By contrast, the marked expansion …


Characterizing The Role Of The T Cell Receptor Repertoire In T Cell Development And Function, Benjamin David Solomon May 2018

Characterizing The Role Of The T Cell Receptor Repertoire In T Cell Development And Function, Benjamin David Solomon

Arts & Sciences Electronic Theses and Dissertations

Expansion and memory of immune cells in response to stimulation of diversified antigen receptors is the hallmark of adaptive immunity. Here, we use antigen receptor sequencing and in vivo analysis of monoclonal cell populations to elucidate the development and function of two T cell populations: Foxp3+RORγt+ CD4+ T cells and γδ T cells. Foxp3+RORγt+ T cells have recently been characterized as an immunoregulatory population highly enriched in the colon lamina propria. However, their developmental origin and relation to RORγt- Treg and RORγt+ TH17 cells remains unclear. Here, we show that despite sharing a subset of TCR specificities with TH17 cells, …


Induction Of Zika Virus-Specific Cd8+ T Cells By Means Of Dna Vaccine, Frank Gambino Jr. Jan 2018

Induction Of Zika Virus-Specific Cd8+ T Cells By Means Of Dna Vaccine, Frank Gambino Jr.

Master's Theses

Zika virus (ZIKV) is a member of the virus family flaviviridae and is transmitted via Aedes aegypti mosquitos. Monoclonal antibodies against dengue virus have been found to cross-react with ZIKV but show no ability to neutralize it. Further studies have shown that Stat2-/- mice given plasma from dengue positive donors exhibit a heightened disease phenotype when challenged with ZIKV. Antibody dependent enhancement is theorized to cause such effect. The goal of this study was to design a plasmid which, when encoded, creates an antigen that will be used to stimulate exclusively CD8+ T cells. The gene sequence of NS3 was …


The Mechanisms Shaping The Repertoire Of Cd4(+)Foxp3(+) Regulatory T Cells, Piotr Kraj, Leszek Ignatowicz Jan 2018

The Mechanisms Shaping The Repertoire Of Cd4(+)Foxp3(+) Regulatory T Cells, Piotr Kraj, Leszek Ignatowicz

Biological Sciences Faculty Publications

Regulatory T (Treg) cells expressing Foxp3 transcription factor control homeostasis of the immune system, antigenic responses to commensal and pathogenic microbiota, and immune responses to self and tumour antigens. The Treg cells differentiate in the thymus, along with conventional CD4+ T cells, in processes of positive and negative selection. Another class of Treg cells is generated in peripheral tissues by inducing Foxp3 expression in conventional CD4+ T cells in response to antigenic stimulation. Both thymic and peripheral generation of Treg cells depends on recognition of peptide/MHC ligands by the T-cell receptors (TCR) expressed on thymic Treg precursors or …