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Generation and Function of CD8 T Cell Memory to γ-Herpesviral Infection

Cush, Stephanie S.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1290802468

Abstract Details

2010, Doctor of Philosophy, Ohio State University, Integrated Biomedical Science Graduate Program.
γ-herpesviruses are a worldwide health concern, and result in a lifelong persistent infection that is associated with some degree of immune control preventing the virus from reactivating and causing disease. However, if this immune control is compromised, γ-herpesviruses can reactivate and cause a variety of tumors in the host. Thus, there is a great need to increase our understanding of the immune response to this family of oncogenic viruses. CD8 T cells have been shown to be critical for viral control. The generation, maintenance, and function of CD8 T cell memory during persistent viral infections is poorly understood. The overall objective of my dissertation is to gain an in depth understanding of CD8 T cell memory generation, maintenance, and function during low load persistent viral infections. We are using a well-established murine model of γ-herpes viral infection, murine gamma herpesvirus 68, or γHV68, to study the in vivo effects of a low load persistent infection on the generation and function of memory CD8 T cells. We determined that virus specific memory CD8 T cells are generated and maintained long term during γHV68 persistence through a variety of phenotypic and functional assays. We found that true bona fide memory CD8 T cells are fully functional during γHV68 latency, which is contrary to other chronic viral infections characterized by high antigenic load. We discovered that the γHV68 specific memory CD8 T cells are capable of surviving in a naïve mouse after adoptive transfer and subsequently proliferating homeostatically in response to cytokines. Additionally, the adoptively transferred memory CD8 T cells have the ability to protect against secondary infection with γHV68. We found heterogeneous virus-specific CD8 T cell memory populations during γHV68 latency, and demonstrated that the terminally differentiated CD8 T cell memory is also equally as functional as the central memory CD8 T cell memory. The current two dominating principles in the field of CD8 T cell memory are: 1) acute infection followed by viral clearance and stable memory formation and 2) persistent infection where there is no viral clearance which leads to T cell dysfunction. My data has contributed to the field of immunology by demonstrating that there is an additional option for how CD8 T cells function during persistent viral infections, where viral persistence does not always lead to memory CD8 T cell dysfunction. Our objective is to gain critical knowledge about CD8 T cell memory to elucidate the possible mechanisms of CD8 T cell function and dysfunction during γHV68 infection. The in vivo model provides relevant information for how memory is generated and maintained in the host, and hopes to offer insights to new therapies and prevention strategies, which is important for many diseases afflicting the human population.
Emilio Flano, PhD (Advisor)
Ginny Sanders, PhD (Other)
Joanne Turner, PhD (Committee Member)
Chris Walker, PhD (Committee Member)
Santiago Partida-Sanchez, PhD (Committee Member)
176 p.
Immunology
T cell; T cell memory

Recommended Citations

Citations

  • Cush, S. S. (2010). Generation and Function of CD8 T Cell Memory to γ-Herpesviral Infection [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1290802468

    APA Style (7th edition)

  • Cush, Stephanie. Generation and Function of CD8 T Cell Memory to γ-Herpesviral Infection. 2010. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1290802468.

    MLA Style (8th edition)

  • Cush, Stephanie. "Generation and Function of CD8 T Cell Memory to γ-Herpesviral Infection." Doctoral dissertation, Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1290802468

    Chicago Manual of Style (17th edition)

osu1290802468
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This open access ETD is published by The Ohio State University and OhioLINK.