The process of lymphocyte migration is fundamental to the function of the immune system. We have pioneered in the development of methodologies to visualize the immune response within the eye at the level of a single cell using intravital microscopy. We have developed models of anterior uveitis and T cells which are transgenic for a specific peptide. To build on our observations to date, we propose to 1) test the hypothesis that specific chemokines, chemokine receptors, and adhesion molecules are involved in the rolling, arrest, and extravasation of T lymphocytes that characterize anterior uveitis;2) test several hypotheses regarding the migration of T cells within the iris stroma at a site of inflammation including characterizing the interaction between T cells and antigen-presenting cells in this site;and 3) test the hypothesis that CDS cells will be fundamentally similar to CD4 cells in their migratory behavior in these models. The studies which we propose will integrate principles of immunology and ophthalmology with technical advances in image analysis and microscropy including the use of image stabilization and two- photon microscopy. These studies should result in a fundamental improvement in the understanding of how T cells behave within a site of inflammation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY013093-09
Application #
7583930
Study Section
Anterior Eye Disease Study Section (AED)
Program Officer
Shen, Grace L
Project Start
1999-09-30
Project End
2011-01-31
Budget Start
2009-02-01
Budget End
2010-01-31
Support Year
9
Fiscal Year
2009
Total Cost
$569,901
Indirect Cost
Name
Oregon Health and Science University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Zhang, Zili; Wu, Xiumei; Duan, Jie et al. (2012) Low dose rapamycin exacerbates autoimmune experimental uveitis. PLoS One 7:e36589
Willermain, François; Rosenbaum, James T; Bodaghi, Bahram et al. (2012) Interplay between innate and adaptive immunity in the development of non-infectious uveitis. Prog Retin Eye Res 31:182-94
Wu, Xiumei; Rosenbaum, James T; Adamus, Grazyna et al. (2011) Activation of OX40 prolongs and exacerbates autoimmune experimental uveitis. Invest Ophthalmol Vis Sci 52:8520-6
Lee, Ellen J; Rosenbaum, James T; Planck, Stephen R (2010) Epifluorescence intravital microscopy of murine corneal dendritic cells. Invest Ophthalmol Vis Sci 51:2101-8
Zhong, Wenwei; Zhang, Zili; Hinrichs, David et al. (2010) OX40 induces CCL20 expression in the context of antigen stimulation: an expanding role of co-stimulatory molecules in chemotaxis. Cytokine 50:253-9
Zhang, Zili; Rosenbaum, James T; Zhong, Wenwei et al. (2010) Costimulation of Th17 cells: Adding fuel or putting out the fire in the inflamed gut? Semin Immunopathol 32:55-70
Myronenko, Andriy; Song, Xubo (2010) Intensity-based image registration by minimizing residual complexity. IEEE Trans Med Imaging 29:1882-91
Rosenzweig, Holly L; Jann, Monica J; Vance, Emily E et al. (2010) Nucleotide-binding oligomerization domain 2 and Toll-like receptor 2 function independently in a murine model of arthritis triggered by intraarticular peptidoglycan. Arthritis Rheum 62:1051-9
Zhang, Zili; Zhong, Wenwei; Hinrichs, David et al. (2010) Activation of OX40 augments Th17 cytokine expression and antigen-specific uveitis. Am J Pathol 177:2912-20
Zhang, Zili; Zhong, Wenwei; Spencer, Doran et al. (2009) Interleukin-17 causes neutrophil mediated inflammation in ovalbumin-induced uveitis in DO11.10 mice. Cytokine 46:79-91

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