GSBS Dissertations and Theses

Approval Date

10-18-2016

Document Type

Doctoral Dissertation

Academic Program

Immunology and Microbiology

Department

Pathology

First Thesis Advisor

Susan Swain, Ph.D.

Keywords

Antigens, CD4-Positive T-Lymphocytes, Human Influenza, Influenza A virus

Subjects

Dissertations, UMMS; Antigens; CD4-Positive T-Lymphocytes; Influenza, Human; Influenza A virus

Abstract

While memory CD4 T cells are critical for effective immunity to pathogens, the mechanisms underlying their generation are poorly defined. Although extensive work has been done to examine the role of antigen (Ag) in shaping memory formation, most studies focus on the requirements during the first few days of the response known as the priming phase. Little is known about whether or not Ag re-encounter by effector T cells (late Ag) alters CD4 memory T cell formation. Since influenza infection produces a large, heterogeneous, protective CD4 memory T cell population, I used this model to examine the role of late Ag in promoting CD4 memory T cell formation.

In the experiments presented in this thesis, I demonstrate that late Ag is required to rescue responding CD4 T cells from default apoptosis and to program the transition to long-lived memory. Responding cells that failed to re-encounter Ag had decreased memory marker expression and failed to produce multiple cytokines upon re-stimulation. Ag recognition is required at a defined stage, as short-term Ag presentation provided 6 days after infection is able to restore canonical memory formation even in the absence of viral infection. Finally, I find that memory CD4 T cell formation following cold-adapted influenza vaccination is boosted when Ag is administered at this stage. These findings imply that persistence of viral Ag presentation into the effector phase is the key factor that determines the efficiency of memory generation. They also suggest that administering Ag during the effector stage may improve vaccine efficacy.

DOI

10.13028/M20W2V

Rights and Permissions

Copyright is held by the author, with all rights reserved.

 
 

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