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dc.contributor.advisorSusan Swain, Ph.D.
dc.contributor.authorBautista, Bianca L.
dc.date2022-08-11T08:08:46.000
dc.date.accessioned2022-08-23T16:07:21Z
dc.date.available2022-08-23T16:07:21Z
dc.date.issued2016-10-18
dc.date.submitted2016-11-23
dc.identifier.doi10.13028/M20W2V
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32232
dc.description.abstractWhile 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.
dc.language.isoen_US
dc.publisherUniversity of Massachusetts Medical School
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectDissertations, UMMS
dc.subjectAntigens
dc.subjectCD4-Positive T-Lymphocytes
dc.subjectInfluenza, Human
dc.subjectInfluenza A virus
dc.subjectAntigens
dc.subjectCD4-Positive T-Lymphocytes
dc.subjectHuman Influenza
dc.subjectInfluenza A virus
dc.subjectImmunology of Infectious Disease
dc.subjectImmunoprophylaxis and Therapy
dc.subjectInfluenza Virus Vaccines
dc.subjectVirus Diseases
dc.titleThe Role of Late Antigen in CD4 Memory T Cell Formation during Influena [i.e. Influenza] Infection: A Dissertation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1839&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/858
dc.legacy.embargo2016-10-24T00:00:00-07:00
dc.identifier.contextkey9411314
refterms.dateFOA2022-08-25T05:08:09Z
html.description.abstract<p>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.</p> <p>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.</p>
dc.identifier.submissionpathgsbs_diss/858
dc.contributor.departmentPathology
dc.description.thesisprogramImmunology and Microbiology


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