Advisor(s)
Paul A Goepfert
Committee Member(s)
William J Britt
David D Chaplin
Robin G Lorenz
Peter E Prevelige
Document Type
Dissertation
Date of Award
2011
Abstract
In the absence of antiretroviral therapy (ART), the majority of individuals infected with human immunodeficiency virus-1 (HIV-1) will develop AIDS. HIV-1-infected controllers are exceptions to the rule; without the use of ART, these individuals spontaneously control virus replication. A better understanding of the immune mechanisms that mediate delayed disease progression, as seen in controllers, will provide valuable insight to the design and development of an effective HIV-1 vaccine. CD8 T cells are important mediators of the antiviral immune response. However, it is unclear which components of the response are critical for long-lasting protection during HIV-1 infection. We first review methods currently used in the analysis of HIV-1-specific CD8 T cell function. We then discuss our analysis of HIV-1-specific CD8 T cell clonal populations that did or did not produce interleukin-2 (IL-2), an effector function associated with delayed disease progression. Having observed a unique clonotypic profile of IL-2 producing CD8 T cells, we predicted that maintenance of IL-2 production identifies a population of CD8 T cells with enhanced ability to (1) produce antiviral soluble factors as observed using multicolor flow cytometry and (2) restrict HIV-1 replication as detected using an in vitro suppression assay (iVSA). To test this hypothesis, we analyzed epitope-specific CD8 T cell function first during chronic HIV-1 infection and subsequently during primary infection. Using the iVSA, we observed significantly enhanced suppression of HIV-1 replication by CD8 T cells derived from controllers when compared to progressors. Interestingly, the level of suppression correlated with a polyfunctional, IL-2+ CD8 T cell response. Preliminary results of CD8 T cell effector function during primary HIV-1 disease show that functional, epitope-specific CD8 T cell lines can be expanded and these cells are able to suppress HIV-1 replication in vitro, albeit to moderate levels. Both the proliferative and suppressive capacity of CD8 T cells derived from the early stage of disease appeared to increase over time. These studies suggest that suppression of HIV-1 replication and polyfunctional IL-2 production would be promising markers of an effective CD8 T cell response and have important implications for the evaluation of HIV-1 vaccine strategies.
ProQuest Publication Number
ISBN
978-1-124-85826-5
Recommended Citation
Akinsiku, Olusimidele Tolulope, "Qualitative Analysis of HIV-1-Specific CD8 T Cell Responses" (2011). All ETDs from UAB. 977.
https://digitalcommons.library.uab.edu/etd-collection/977
Comments
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