dc.contributor.advisor | Benedict, Stephen H. | |
dc.contributor.author | Dotson, Abby L. | |
dc.date.accessioned | 2012-10-28T16:38:18Z | |
dc.date.available | 2012-10-28T16:38:18Z | |
dc.date.issued | 2012-05-31 | |
dc.date.submitted | 2012 | |
dc.identifier.other | http://dissertations.umi.com/ku:12162 | |
dc.identifier.uri | http://hdl.handle.net/1808/10299 | |
dc.description.abstract | CD4+ T cells are essential for proper function of the immune system. Many facets of an immune response are dependent on help from CD4+ T cells to become activated and exhibit effector function. Memory CD4+ T cells are a differentiated subset of T helper cells that give rise to long-lasted protective immunity. Differentiation to a memory phenotype from a naïve T cell that has never encountered antigen requires two signals. Costimulatory molecules send a second signal into naïve T cells that follows stimulation of the T cell receptor and greatly affects how naïve T cells activate and differentiate. The present work centers on the ability of the costimulatory molecule Intercellular Adhesion Molecile-1 (ICAM-1) to induce activation and differentiation of CD4+ naïve T cells to effector and memory phenotypes. We observed that costimulation through ICAM-1 generates a central memory-like population that is capable of migration to the lymph nodes and to a lesser extent the intestine. ICAM-1 costimulation is also capable of inducing memory differentiation after a short duration of signal but long-term costimulation is needed to generate a sizable population. In addition, costimulation of CD4+ naïve T cells from older individuals through ICAM-1 is able to produce memory cells more so than other costimulatory molecules. This suggesting that ICAM-1 could be utilized to help restore immune function during senescence. ICAM-1 and its ligand leukocyte function-associated antigen-1 (LFA-1) also provide targets for blocking self-reactive T cells in autoimmune diseases. Peptides against ICAM-1 and LFA-1 were used in the type I diabetes NOD mouse model. We observed a significant delay in symptoms with therapeutically treated mice compared to saline control mice and stopped T cell infiltration of the pancreatic islets. Additionally, T cells from treated mice were no longer able to respond to β-cell antigen indicating a shut down of the autoreactive immune response. | |
dc.format.extent | 266 pages | |
dc.language.iso | en | |
dc.publisher | University of Kansas | |
dc.rights | This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author. | |
dc.subject | Microbiology | |
dc.subject | Immunology | |
dc.subject | Differentiation | |
dc.subject | Icam-1 | |
dc.subject | T cellS | |
dc.subject | Therapy | |
dc.subject | Type 1 diabetes | |
dc.title | Intercellular Adhesion Molecule-1 in T cell differentiation and as a target for peptide therapy of type 1 diabetes | |
dc.type | Dissertation | |
dc.contributor.cmtemember | Benedict, Stephen H. | |
dc.contributor.cmtemember | Davido, David O. | |
dc.contributor.cmtemember | Ragen, Ron | |
dc.contributor.cmtemember | Stetler, Dean A. | |
dc.contributor.cmtemember | Yankee, Thomas | |
dc.thesis.degreeDiscipline | Molecular Biosciences | |
dc.thesis.degreeLevel | Ph.D. | |
dc.rights.accessrights | openAccess | |