Human vasculitis is a common disease entity. Currently the only known cause of autoimmune vasculitis is immune complex deposition which has been demonstrated in some types of vasculitis but not in others. A lymphocyte-mediated pathogenesis has been suspected but not proven in some vasculitides, especially those occurring in conjunction with collagen-vascular diseases. Nor has a model for an autoimmune cellular vasculitis been developed to the best of our knowledge. We plan to address this gap through the further development of a murine model of autoimmune vasculitis. In this model, lymphocytes are co-cultured with syngeneic endothelium or smooth muscle. After activation, the lymphocytes are injected into syngeneic hosts with a resultant vasculitis seen in various organs. It is hypothesized that either the lympocytes are activated to surface antigens in co-culture and then cross-react with cells in vivo or that the lymphocytes escape normal suppressor regulation by being co-cultured in vitro, or both. The objectives of this project are to further develop this model of autoimmune vasculitis while at the same time addressing some of the pathogenic immune mechanisms which allow the lesions to develop.
The specific aims of this project are to: 1) enhance the number and severity of vasculitis lesions by attenuating suppressor cell systems in culture and in the hosts through the use of cytoxan, irradiation and anti-IJ+ sera; 2) to determine the phenotypes of cells in the lesions as well as the role of immunoglobulin and complement; 3) to investigate the relative contributions to the lessions of injected lymphocytes versus host lymphocytes; 4) to assess the morphologic types of cells in he lesions as well as the vascular damage by electron microscopy; 5) attempt to clone activated, effector T-cells; and 6) to identify the stimulating antigen(s) in the co-culture system.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL031944-02
Application #
3343125
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1984-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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Hart, M N; Fabry, Z; Love-Homan, L et al. (1992) Brain microvascular smooth muscle and endothelial cells produce granulocyte macrophage colony-stimulating factor and support colony formation of granulocyte-macrophage-like cells. Am J Pathol 141:421-7
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Bar, R S; Boes, M; Booth, B A et al. (1989) The effects of platelet-derived growth factor in cultured microvessel endothelial cells. Endocrinology 124:1841-8
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Hart, M N; Linthicum, D S; Waldschmidt, M M et al. (1987) Experimental autoimmune inflammatory myopathy. J Neuropathol Exp Neurol 46:511-21

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