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dc.contributor.authorOu, Rong
dc.date.accessioned2021-03-28T17:39:48Z
dc.date.available2021-03-28T17:39:48Z
dc.date.issued2004-07
dc.identifier.urien
dc.identifier.urihttp://hdl.handle.net/10675.2/623931
dc.description.abstractThe murine LCMV system provides a classic model to study the mechanism of immunological tolerance, an efficient strategy used by virus to establish a persistent infection by selective down-regulation of virus-specific T lymphocytes. High viral burden in the onset of infection drives responding cells into functional unresposiveness (anergy) that can be followed by their physical elimination. In this study, the downregulation of the virus-specific CDS+-T -cell response was' studied during a persistent infection of adult mice, with particular emphasis on the contribution of the interferon response in promoting host defense, or perforin-, Fas/FasL-, or TNFRI-mediated cytolysis in regulating T -cell homeostasis. Since LCMV infects a broad range of host tissues, the functional properties of virus-specific CDS+ T cells in different tissues during LCMV infection were also evaluated. Infection of mice deficient in receptor for type I (IFN-a/~), type II (IFN-y), or both type I and II IFNs with LCMV isolates that vary in their capacity to induce T -cell exhaustion, revealed a critical role for IFN-a/~ in restricting LCMV spread at the onset of infection while IFN-y has impact on effector cells. The production of IFN-a./~ and/or IFN-y critically regulates the virus-host balance during the acute phase of infection, such that a high viral burden drives responding cells into different programs of exhaustion. Infection of mice deficient in perferin, FasL or TNFRI with the Docile or Aggressive strains of LCMV revealed comparable kinetics of expansion and functional inactivation of virusspecific CDs+ T cells in the early phase of infection in C5 7 BL/6 controls. However, the data underscore a critical role for these molecules in the persistence of the virus-specific ens+-T-cell population once it has become anergic. Study of the functional properties of virus-specific ens+ T cells in different tissues during LeMV infections showed that a central role for the viral load in lymphoid tissue in the induction and maintenance of clonal exhaustion. The <;lata strongly suggest that ens+ T cells may be differentially regulated in the environments of lymphoid versus nonlymphoid tissues, and the pattern of T cell exhaustion observed with mice is likely a common feature ofthe immune response during chronic infections in humans.en_US
dc.language.isoen_USen_US
dc.publisherAugusta Universityen_US
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en_US
dc.subjectLCMVen_US
dc.subjectIFNsen_US
dc.subjectPerforinen_US
dc.titleT cell immune response in persistent infection of lymphocytic choriomeningitis virus (LCMVen_US
dc.typeDissertationen_US
dc.contributor.departmentMedical College of Georgiaen_US
dc.description.advisorN/A, N/A
dc.description.committeeN/A, N/A
dc.description.degreeDoctor of Philosophyen_US
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refterms.dateFOA2021-03-28T17:39:49Z


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