Browsing by Subject "CD4 T cells"

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    CD4 T cells in the protection and pathogenesis of persistent Salmonella infection
    (2010-10) Johanns, Tanner Michael
    CD4 T cells contribute a diverse and non-redundant role to host defense against infections by orchestrating the activation and quality of the innate and adaptive immune responses. The diversity of CD4 T cell function is accomplished by differentiating into a plethora of distinct effector and regulatory lineages that dictate the kinetics and extent of immune activation. However, due to the range and breadth of CD4 T cell function, the precise role and mechanism of these various effector and regulatory subsets in host immunity remains incompletely understood. As persistent infections represent a significant source of morbidity and mortality worldwide, and CD4 T cells play a critical role in protection against this class of pathogens, we sought to elucidate the relative contribution of effector and regulatory CD4 T cell subsets in the pathogenesis and protection of this class of pathogens. Using a murine model of persistent Salmonella infection, we demonstrate that CD4 T cells are required for protection during primary infection but dispensable for secondary immunity. Moreover, both host and pathogen factors limit the generation of a protective effector CD4 T cell response during primary disease including increased regulatory CD4 T cell suppressive function and Salmonella-associated virulence genes, respectively, that enables establishment and persistence of disease. Together, these findings provide novel insight into disease process of persistent Salmonella infection that will aid in the design of future therapeutic and prevention strategies.
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    Impaired CD4 T Cell-Mediated Immunity After Sepsis
    (2020-08) Sjaastad, Frances
    It is estimated that 1.7 million Americans suffer from sepsis every year. While improvements in intensive care over the last 30 years have reduced mortality from the initial septic event from 80% to 10-20%, sepsis survivors suffer from a functional impairment of the immune system resulting in increased susceptibility to secondary infection that can last for years. In fact, approximately 70% of sepsis related deaths are due to secondary infection that occurs after the initial septic event as result of immunosuppression. While our understanding of sepsis has grown and improved over the last several decades, there are currently no approved targeted therapies for treatment of the dysregulated host response to the initial infection or the subsequent sepsis induced immune suppression. An improvement of our understanding of the mechanisms responsible for the dysregulated host response to infection and the immunosuppression observed after sepsis will be critical for developing effective therapies and improving the survival and quality of life for septic patients. Previous research has found that despite the transient nature of the CD4 T cell compartment depletion, recovery is uneven when looking at naïve antigen specific populations. Furthermore, it is unknown what impact this uneven recovery has on immunization responses, including CD4 T cell-dependent B cell responses, and how recovery occurs in memory populations of antigen specific CD4 T cells. In the following studies, we have investigated the hypothesis that alterations in the number and function of antigen specific populations of CD4 T cells after sublethal CLP-induced sepsis are responsible for the suppressed immunity that leads to increased mortality from secondary infection in sepsis survivors. Additionally, we have investigated inflammatory responses and CD4 T cell compartment depletion in an immune experienced mouse using various models of sepsis. Through these efforts we have uncovered evidence of innate immune training in the cohoused immune experienced mouse which heightens inflammatory responses and reduces survival following sepsis onset. Our rationale for these studies is that once we understand how immune experience influences inflammatory responses and cells within the adaptive immune system are affected during sepsis, we will be able to develop new and innovative therapeutic approaches to restore immune cell numbers and function in sepsis survivors.