The Role of Late Antigen in CD4 Memory T Cell Formation during Influena [i.e. Influenza] Infection: A Dissertation
Authors
Bautista, Bianca L.Faculty Advisor
Susan Swain, Ph.D.Academic Program
Immunology and MicrobiologyUMass Chan Affiliations
PathologyDocument Type
Doctoral DissertationPublication Date
2016-10-18Keywords
Dissertations, UMMSAntigens
CD4-Positive T-Lymphocytes
Influenza, Human
Influenza A virus
Antigens
CD4-Positive T-Lymphocytes
Human Influenza
Influenza A virus
Immunology of Infectious Disease
Immunoprophylaxis and Therapy
Influenza Virus Vaccines
Virus Diseases
Metadata
Show full item recordAbstract
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/M20W2VPermanent Link to this Item
http://hdl.handle.net/20.500.14038/32232Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/M20W2V
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