Year: 2009
Type: article
Abstract: T cell-mediated pathology is a major cause of disease in both infection and autoimmunity.While T cell responses provide protection from pathogens, uncontrolled responses can lead to rampant autoimmunity and immunopathology.In this dissertation, we employed a mouse model of central nervous system (CNS) viral infection to further understand the role and regulation of CD4+ T cell responses in immunopathology.In this model, intracranial (i.c.) infection of immunocompetent mice with lymphocytic choriomeningitis virus (LCMV) results in fatal meningitis mediated by CD8+ T cells by day 8 post-infection.I.c.LCMV infection of mice deficient in CD8+ T cells, either by deficiency in β 2 microglobulin (β 2 m -/-) or in vivo depletion, results in less severe meningitis and lower mortality rate.CD8+ T cell-deficient mice also develop severe anorexia and weight loss; these symptoms, as well as meningitis, are mediated by anti-viral CD4+ T cell responses and are not affected by viral titer.Thus, this mouse model allows us to directly examine: (i) factors that influence immunopathologic CD4+ T cell responses to viral infection; and (ii) mechanism(s) downstream of CD4+ T cell responses that control immunopathologic disease.Identification of mechanism(s) that control the magnitude and downstream sequelae of the viral-specific CD4+ T cell response will enhance our understanding of the regulation of and our ability to treat immunopathologic disease.This dissertation investigated three main hypotheses: (i) androgens and NKT cells independently regulate the quantity and quality of viral-specific CD4+ T cell responses; (ii) type I interferon signaling controls the activation of NKT cells during viral infection; and (iii) type II interferon (IFN-γ) signaling controls recruitment and activation of antigen-presenting cells (APCs) but not viral-specific CD4+ T cell responses.Our work shows that CD4+ T cell PREFACE This thesis consists of an introduction (Chapter 1), two completed manuscripts (Chapters 2 and 4) and two manuscripts near completion (Chapters 3 and 5), all of which are organized as individual manuscripts, and a summary (Chapter 6).The work presented herein was performed
Author: Adora Lin
Institution: University of Cincinnati
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2254750418