Over the past few years, transplantation of different organs has become routine from a technical point of view. There remain, however, two major unresolved obstacles--graft rejection, and/or the side effects of immunosuppressive drugs, and an inadequate source of donated organs. The obstacle of a limited supply is so severe that many potential recipients succumb while awaiting a suitable donor. Although numerous avenues should be pursued in an effort to eliminate these shortages, the one that excites us most is the possibility of xenotransplantation. Because of availability, cattle or pigs may be the ultimate donor source. However, for xenotransplantation to have any possibility of succeeding initially, we believe it will require that donor animals be other primates. Even though cardiac allotransplantation is quite successful, many fundamental issues remain to be assessed before xenotransplantation can be viewed as practical. Because of the tremendous number of inbred strains of mice and rats with defined genetics, they have been exceedingly valuable in defining immune reactivities that underlie mechanisms of allograft rejection/acceptance. Based on this information, it is advantageous to continue to utilize this genetic material in studies on any of a number of fundamental aspects of xenograft rejection/acceptance. Specifically, the aims of this proposal are to: (a) characterize the cell-types involved in a cell-mediated mouse/rat model of xenograft rejection; (b) characterize antibodies that underlie both hyperacute and chronic rejection of xenografts; and (c) assess genetic controls that are manifested at the level of the recipient as well as the donor on rejection/acceptance of xenografts.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI027331-02
Application #
3141539
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1990-09-30
Project End
1993-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Wisconsin River Falls
Department
Type
Schools of Arts and Sciences
DUNS #
City
River Falls
State
WI
Country
United States
Zip Code
54022
Click, Robert E (2014) Alteration of radiation-sensitive processes associated with cancer and longevity by dietary 2-mercaptoethanol. J Cancer Res Ther 10:127-32
Click, Robert E (2014) Review: 2-mercaptoethanol alteration of in vitro immune functions of species other than murine. J Immunol Methods 402:1-8
Click, Robert E (2013) Anticancer activity and chemoprevention of xenobiotic organosulfurs in preclinical model systems. Oncol Discov 1:
Click, Robert E (2012) A Potential 'Curative' Modality for Crohn's Disease---Modeled after Prophylaxis of Bovine Johne's Disease. Mycobact Dis 2:117
Click, Robert E (2011) A 60-day probiotic protocol with Dietzia subsp. C79793-74 prevents development of Johne's disease parameters after in utero and/or neonatal MAP infection. Virulence 2:337-47
Click, Robert E (2011) Successful treatment of asymptomatic or clinically terminal bovine Mycobacterium avium subspecies paratuberculosis infection (Johne's disease) with the bacterium Dietzia used as a probiotic alone or in combination with dexamethasone: Adaption to chronic h Virulence 2:131-43
Click, Robert E; Van Kampen, Craig L (2010) Comparison of ante-mortem assays to assess progression/regression of paratuberculosis in individual dairy animals. Virulence 1:134-44
Click, Robert E; Van Kampen, Craig L (2010) Assessment of Dietzia subsp. C79793-74 for treatment of cattle with evidence of paratuberculosis. Virulence 1:145-55
Click, R E; Van Kampen, C L (2009) Short communication: progression of Johne's disease curtailed by a probiotic. J Dairy Sci 92:4846-51
Sakakibara, N; Jamieson, S W; Wolf, P et al. (1995) Rejection of rat cardiac xenografts by mouse CD4 or CD8 T cells. Transplant Proc 27:264-5

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