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Effector and Regulatory CD4 T cells During Mycobacterium tuberculosis infection

Green, Angela Marie (2010) Effector and Regulatory CD4 T cells During Mycobacterium tuberculosis infection. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Mycobacterium tuberculosis continues to be a leading cause of death by an infectious agent world wide with approximately two million deaths attributable to it annually. Once infected, the host mounts a robust Th1 type immune response that contains, but does not eliminate the bacteria. A small percentage (5-10%) fail to contain the infection, develop active disease, and are contagious. Most remain asymptomatic and are considered latently infected. BCG, while the gold standard for vaccination, ultimately appears to limit disease, but not prevent infection. In addition, chemotherapeutic treatment is long, requires multiple agents, and compliance is difficult to maintain. With one third the world's population infected, inadequate vaccine efficacy, and difficult treatment regimen, it is imperative that a better understanding of which factors are responsible for containment of the infection be achieved. CD4 T cells are an essential component of the immune response that controls M. tuberculosis. CD4 T cells are able to both promote inflammation and dampen its effect. As a pro-inflammatory Th1 cell, these cells secrete pro-inflammatory cytokines, participate in macrophage and dendritic cell activation and help prime CD8 T cells. As regulatory T cells, CD4 T cells prevent autoimmunity and may act to protect surrounding tissue from immunopathologic damage. One main function of pro-inflammatory CD4 T cells is IFNγ production, however other cells can and do produce IFNγ. In addition, the role of regulatory T cells during infection and how they relate to disease progression has yet to be elucidated. The work presented in this dissertation provides a new model for addressing the role of IFNγ from sources other than CD4 T cells, and addresses what pro-inflammatory functions they may have in addition to IFNγ production. In addition, these studies address regulatory T cells and the anti-inflammatory effects of long term IL-12 treatment as well as Treg's relationship to disease outcome in non-human primates.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Green, Angela Marieagreen@pitt.eduAGREEN
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairFlynn, JoAnne Ljoanne@pitt.eduJOANNE
Committee MemberRay, Anuradharaya@pitt.eduRAYA
Committee MemberNau, Gerard Jgjnau@pitt.eduGJNAU
Committee MemberNorris, Karen Akan1@pitt.eduKAN1
Committee MemberHendricks, Robert
Date: 23 December 2010
Date Type: Completion
Defense Date: 7 October 2010
Approval Date: 23 December 2010
Submission Date: 22 December 2010
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Molecular Virology and Microbiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: CD4 T cell; mouse; Mycobacterium tuberculosis; non-human primate; Regulatory T cell; tuberculosis
Other ID:, etd-12222010-135410
Date Deposited: 10 Nov 2011 20:11
Last Modified: 15 Nov 2016 13:55


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