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Intercellular Adhesion Molecule-1 in T cell differentiation and as a target for peptide therapy of type 1 diabetes
Dotson, Abby L.
Dotson, Abby L.
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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.
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Date
2012-05-31
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University of Kansas
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Keywords
Microbiology, Immunology, Differentiation, Icam-1, T cellS, Therapy, Type 1 diabetes