All ETDs from UAB

Advisory Committee Chair

Scott Barnum

Advisory Committee Members

Dan Bullard

Kurt Zinn

Vithal Ghanta

Pete Burrows

Document Type

Dissertation

Date of Award

2007

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Lymphocytes are highly mobile cells that can travel throughout the body in response to a multitude of stimuli. Identifying lymphocyte trafficking patterns in vivo is essential for a complete understanding of immune function. Cell-cell and cell-tissue interactions in immune development and in lymphocyte response to stimuli can be comprehended with these investigations. Although the location of cell populations in various tissues at any given point in time may be investigated by techniques such as flow cytometry and immunofluorescence, these methods are not easily used in the assessment of dynamic cell migration patterns in vivo. In the past years, technologies for imagaing molecular and cellular changes in living animals have advanced to a point where it is possible to reveal the migratory paths of these cells. In this dissertation, we utilize these imaging techniques to develop a Luciferase reporter transgenic mouse, T-lux. The T-lux mouse expresses the enzyme Luciferase exclusively in T cells. This model system allowed for the visual investigation of CD4+ and CD8+ specific antigen response to the Ovalbumin (OVA) peptide. By delineating their kinetics and migration patterns in vivo in real time we can assess the similarities and differences of these two subpopulations of lymphocytes. We next studied the autoreactive T cell response in the autoimmune demyelinating disease, Experimental Autoimmune Encephalomyelitis (EAE). We could iii visualize the trafficking of MOG-sensitzed T cells into CNS-draining lymph nodes and eventual infiltration into the brain and spinal cord.

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