Vaccinia and Dengue viruses : exploring current fundamental issues of memory T cells and utilizing comparative quantitative immunology to compare correlates of protection following smallpox immunization.
Year: 2008
Type: article
Abstract: Memory T cells often perform an important role in mediating viral clearance upon secondary viral infection.Therefore, expanding the current understanding of issues surrounding memory T cell development, the long term maintenance and the functional characteristics of different memory subsets is essential.A deeper understanding of these issues surrounding memory T cells will aid in generating more successful vaccines.The unsuccessful attempts to create vaccines to protect against devastating diseases such as HIV and malaria have highlighted the flaws in traditional approaches of developing empirically derived vaccines.Data obtained from the following studies can be used and applied to rationally attain new, 21 st century vaccines.The work presented here focuses on two viruses, vaccinia and Dengue.However, the questions addressed have implications beyond these two pathogens.Here we present findings on the long term maintenance and functional properties of effector and central memory T cells in humans last vaccinated with vaccinia virus over 30 years previously.These data provides a basis for a quantitative immunological comparison after administration of new smallpox vaccines.Utilizing a mouse model of vaccinia infection, we then address how antigen duration and the induction of inflammation effects memory T cell development.Finally, the four serotyes of Dengue virus provided us with an opportunity to study heterologous infection and the possible detrimental effects of partial T cell agonists on memory T cells.x contribute to the development of Dengue Hemorrhagic Fever (DHF) in order to provide information that can be used to develop an effective vaccine.Moreover, this work with the MRCE, using both Vaccinia virus and Dengue virus, provided us with an opportunity to make a substantial contribution to the current understanding of fundamental issues surrounding memory T cells following acute viral infections.Some of the issues addressed included questions regarding memory T cell development and their long-term maintenance, further descriptions of the functional characteristics and phenotypes of different memory cell subsets and issues of variant peptide ligands and cross-reactivity.Scientific inquiry into these topics has not only aided our lab and other labs of the MRCE in developing a better understanding of Orthopox and Dengue virus immunogenicity, but have also had implications to the broader scientific community interested in issues of memory T cell immunology.Specific Aims: 1) Determine the frequency and functional properties of the various memories CD8 + T cell subsets present in individuals previously vaccinated against smallpox 2) Establish the effect of enhanced stimulation through antigenic load and inflammation in directing the development of T cell effector memory and central memory after infection of mice with various preparations of vaccinia virus that differ in their replicative capacity and immunogenicity 3) Refine the mouse model of heterolgous secondary Dengue Virus infection, focusing on the memory T cell's role in causing serotype cross-reactivity leading to altered cytokine profiles and severe immunopathogenesis * Our efforts at CWRU were focused on T cells, mainly CD8 + T cells, while other groups within the MRCE were focused on CD4 + T cells and antibodies.This was done in accordance with MRCE policy to prevent competition among MRCE members and minimize unneccesary experimental overlap.
Author: Nicholas Daniel Ostrout
Institution: Case Western Reserve University
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2311264011