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Dissertation
Stimulation of CD8+ T cell responses to influenza A virus
Doctor of Philosophy (Ph.D.), Drexel University
Feb 2007
DOI:
https://doi.org/10.17918/00000660
Abstract
CD8+ T cells are a critical component of the host response to viral infections. However, much of the mechanism by which CD8+ T cell responses are initiated and maintained are not yet known. Interactions between the innate immune system and the adaptive immune system are critical in the development of the antigen-specific CD8+ T cell response. Not the least of these interactions is costimulation provided by dendritic cells and other antigen-presenting cells. T cells that develop in the absence of costimulation are less able to respond to antigen in the context of viral infection. CD27 is a critical member of the costimulatory cascade required during the primary CD8+ T cell response. In this thesis, the role of CD27 stimulation as a survival factor, preventing apoptosis during the later phase of the influenza-specific CD8+ T cell response was described. The function of CD27 is mediated through CD4+ T cells and modulates the signal from Fas-FasL interactions. CD27 signaling is also required for the quality of CD8+ T cell memory as blocking CD27L during the primary response impairs memory CD8+ T cell expansion in response to subsequent infection. CD28 is also important during the later phase of the primary CD8+ T cell response. Signals of CD28 are required directly by CD8+ T cells, independent of CD4+ T cell help or signals from Fas or TRAIL. This thesis clarifies the roles of both CD27 and CD28 costimulation in an anti-viral CD8+ T cell response. Differences between these two costimulatory molecules and how they influence the later stages of a CD8+ T cell response have been elucidated. This thesis demonstrates the importance of understanding the mechanisms of costimulation in modulating CD8+ T cell responses and they may effect immune protection.
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Details
- Title
- Stimulation of CD8+ T cell responses to influenza A virus
- Creators
- Douglas V. Dolfi
- Contributors
- Peter D. Katsikis (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xi, 153 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 991014970194504721