Abstract

This is a competitive renewal grant request for continued studies of vasculitis, a disease of humans frequently associated with collagen-vascular type autoimmune diseases. The murine model to be exploited is one in which splenic cells are co-cultured in vitro with syngeneic microvascular smooth muscle (SM) followed by transfer of the activated (immunized) cells into syngeneic recipients resulting in a distinct vasculitis. Preliminary studies have shown strong MHC restriction (syngeneic response much greater than allogeneic) governing spleen cell activation to SM that can be blocked by anti-Ia in vitro. The hypothesis to be tested is that lymphocytes recognize SM and MHC antigens in vitro to become activated. After transfer into syngeneic hosts the lymphocytes recruit cells that also recognize SM and MHC antigens in attacking vascular SM. This proposal will address both the in vitro lymphocyte activation events as well as the in vivo effector events in the host mice.
Specific aims related to in vitro events include determination of mRNA for class 11 antigen in SM with the use of cDNA probes and determination of whether SM can present antigen to antigen-specific T cell clones.
Specific aims related to the effector (in vivo) events include determination of the possible role of SM specific antibodies in affected mice and determination of the effector cell(s) in the lesions by light and electron microscopy. Several SM activated lymphocyte clones (L3 T4+ and Lyt 2+) have been developed and will be used to determine their ability to elicit vasculitis as well as their specificity for SM.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL031944-04A1
Application #
3343123
Study Section
Pathology A Study Section (PTHA)
Project Start
1984-04-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242

  Publications

Fabry, Z; Waldschmidt, M M; Hendrickson, D et al. (1992) Adhesion molecules on murine brain microvascular endothelial cells: expression and regulation of ICAM-1 and Lgp 55. J Neuroimmunol 36:1-11
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
Waldschmidt, M M; Fabry, Z; Keiner, J et al. (1991) Adhesion of splenocytes to brain microvascular endothelium in the BALB/c and SJL/j mouse systems. J Neuroimmunol 35:191-200
Mitchell, G W; Williams, G S; Bosch, E P et al. (1991) Class II antigen expression in peripheral neuropathies. J Neurol Sci 102:170-6
Hart, M N; Fabry, Z; Waldschmidt, M et al. (1990) Lymphocyte interacting adhesion molecules on brain microvascular cells. Mol Immunol 27:1355-9
Fabry, Z; Waldschmidt, M M; Moore, S A et al. (1990) Antigen presentation by brain microvessel smooth muscle and endothelium. J Neuroimmunol 28:63-71
Fabry, Z; Waldschmidt, M M; Van Dyk, L et al. (1990) Activation of CD4+ lymphocytes by syngeneic brain microvascular smooth muscle cells. J Immunol 145:1099-104
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
Hart, M N; Merz, P; Bennett-Gray, J et al. (1988) beta-amyloid protein of Alzheimer's disease is found in cerebral and spinal cord vascular malformations. Am J Pathol 132:167-72
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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