T Cell Immune Response in Persistent Infection of Lymphocytic Choriomeningitis Virus (LCMV)

Hdl Handle:
http://hdl.handle.net/10675.2/554090
Title:
T Cell Immune Response in Persistent Infection of Lymphocytic Choriomeningitis Virus (LCMV)
Authors:
Ou, Rong
Abstract:
The m urine LCMV system provides a ciassic 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 o f infection drives responding cells into functional unresposiveness (anergy) that can, be followed by their physical elimination. In this study, the downregulation o f the virus-specific CD8^-T-ceil response was studied during a persistent infection o f adult mice, with particular emphasis on the contribution of the interferon response in promoting host defense, or perforin-, Fas/FasL-, or TN FR l-m ediated cytolysis in regulating T-cell homeostasis. Since LCMV infects a broad range o f host tissues, the functional properties o f virus-specific CD8'^ T cells in different tissues during LCMV infection were also evaluated. Infection of mice deficient in receptor for type I (IFN-a/p), type II (IFN-y), or both type I and II IFNs with LCMV isolates that vary in their capacity to induce T-celi exhaustion, revealed a critical role for IFN -a/p in restricting LCMV spread at the onset o f infection while IFN-y has impact on effector cells. The production o f IF N -a/p and/or IFN-y critically regulates the virus-host balance during the acute phase o f infection, such that a high viral burden drives responding cells into different programs o f exhaustion. Infection o f mice deficient in perferin, FasL or TNFRl with the Docile or Aggressive strains of LCMV revealed comparable kinetics of expansion and functional inactivation o f virusspecific C D ^ T cells in the early phase o f Infection in C57BL/6 controls. However, the data underscore a critical role for these molecules in the persistence o f the virus-specific CD8"‘-T-ceil population once it has become anergic. Study o f the functional properties of virus-specific CD8'^ T cells in different tissues during LCMV infections showed that a centra! role for the viral load in lymphoid tissue in the induction and maintenance of clonal exhaustion. The data strongly suggest that CD8^ T ceils may be differentially regulated in the environments o f lymphoid versus nonlymphoid tissues, and the pattern of T cell exhaustion observed with mice is likely a common feature o f the immune response during chronic infections in humans.
Affiliation:
GRU Cancer Center
Issue Date:
Jul-2004
URI:
http://hdl.handle.net/10675.2/554090
Additional Links:
http://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/305100626?accountid=12365
Type:
Dissertation
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorOu, Rongen
dc.date.accessioned2015-05-18T19:37:13Zen
dc.date.available2015-05-18T19:37:13Zen
dc.date.issued2004-07en
dc.identifier.urihttp://hdl.handle.net/10675.2/554090en
dc.description.abstractThe m urine LCMV system provides a ciassic 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 o f infection drives responding cells into functional unresposiveness (anergy) that can, be followed by their physical elimination. In this study, the downregulation o f the virus-specific CD8^-T-ceil response was studied during a persistent infection o f adult mice, with particular emphasis on the contribution of the interferon response in promoting host defense, or perforin-, Fas/FasL-, or TN FR l-m ediated cytolysis in regulating T-cell homeostasis. Since LCMV infects a broad range o f host tissues, the functional properties o f virus-specific CD8'^ T cells in different tissues during LCMV infection were also evaluated. Infection of mice deficient in receptor for type I (IFN-a/p), type II (IFN-y), or both type I and II IFNs with LCMV isolates that vary in their capacity to induce T-celi exhaustion, revealed a critical role for IFN -a/p in restricting LCMV spread at the onset o f infection while IFN-y has impact on effector cells. The production o f IF N -a/p and/or IFN-y critically regulates the virus-host balance during the acute phase o f infection, such that a high viral burden drives responding cells into different programs o f exhaustion. Infection o f mice deficient in perferin, FasL or TNFRl with the Docile or Aggressive strains of LCMV revealed comparable kinetics of expansion and functional inactivation o f virusspecific C D ^ T cells in the early phase o f Infection in C57BL/6 controls. However, the data underscore a critical role for these molecules in the persistence o f the virus-specific CD8"‘-T-ceil population once it has become anergic. Study o f the functional properties of virus-specific CD8'^ T cells in different tissues during LCMV infections showed that a centra! role for the viral load in lymphoid tissue in the induction and maintenance of clonal exhaustion. The data strongly suggest that CD8^ T ceils may be differentially regulated in the environments o f lymphoid versus nonlymphoid tissues, and the pattern of T cell exhaustion observed with mice is likely a common feature o f the immune response during chronic infections in humans.en
dc.relation.urlhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/305100626?accountid=12365en
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
dc.subjectLCMVen
dc.subjectIFNsen
dc.subjectPerforinen
dc.subjectFas/FasLen
dc.subjectTNFR1en
dc.subjectT Cell Exhaustionen
dc.subjectNonlymphoid Tissuesen
dc.titleT Cell Immune Response in Persistent Infection of Lymphocytic Choriomeningitis Virus (LCMV)en
dc.typeDissertationen
dc.contributor.departmentGRU Cancer Centeren
dc.description.advisorMoskophidis, Demetriusen
dc.description.committeeMivechi, Nahid; Sarkar, Nurul; Tuan, Dorothy; Horuzsko, Anatolijen
dc.description.degreeDoctor of Philosophy (Ph.D.)en
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