The objectives of the project are to determine if some of the minor histocompatibility antigens expressed on mouse epidermal cells represent unique, tissue-specific determinants. This will be accomplished by using epidermal cells prepared by trypsinization of adult mouse tail skin as stimulators and targets of lymphocyte-mediated cytotoxicity. The genetic control of the cytotoxicity evoked by antigens expressed by epidermal cells will be characterized. In addition, clones of cytotoxic T lymphocytes generated by immunization with allogeneic epidermal cells will be maintained in continuous culture with the use of T-cell growth factor. The specificity of these monoclonal effector cells will be determined by techniques such as cold-target inhibition and antigen-driven suicide. In addition, their ability to mediate specific skin allograft rejection and skin lesions in graft-versus-host reactions will be determined in vivo by adoptive transfer techniques; the objective here being to determine whether epidermal-specific antigens identified in vitro are responsible for the unusual vulnerability of skin allografts to rejection, on the one hand, and the primary role of the skin as a target tissue in graft-versus-host-disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI023653-02
Application #
3135923
Study Section
Immunobiology Study Section (IMB)
Project Start
1985-12-01
Project End
1987-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Steinmuller, D; Snider, M E; Noble, R L et al. (1991) The murine immune lymphocyte transfer reaction revisited. Transplant Proc 23:163-4
Steinmuller, D; Wakely, E; Landas, S K (1991) Evidence that epidermal alloantigen Epa-1 is an immunogen for murine heart as well as skin allograft rejection. Transplantation 51:459-63
Steinmuller, D; Snider, M E; Noble, R L et al. (1990) Dissociation of tissue destruction induced by cytolytic T cells in vivo and cytotoxicity as measured in vitro. Transplantation 50:663-8
Noble, R L; Steinmuller, D (1989) Blocking of interleukin-2 production, but not the tissue destruction induced by cytotoxic T cells, by cyclosporine. Transplantation 47:322-6
Steinmuller, D; Tyler, J D; Snider, M E et al. (1988) Tissue destruction resulting from the interaction of cytotoxic T cells and their targets. Ann N Y Acad Sci 532:106-18
Hadley, G A; Steinmuller, D (1988) Domination by epidermal cell-reactive autoantibodies in attempts to raise antibodies to Epa-1 alloantigens. Transplantation 45:215-21
Hadley, G A; Marcelo, C L; Steinmuller, D (1988) Monoclonal antibodies to tissue-restricted autoantigens in the mouse epidermis. Hybridoma 7:441-51
Snider, M E; Steinmuller, D (1987) Nonspecific tissue destruction as a consequence of cytotoxic T lymphocyte interaction with antigen-specific target cells. Transplant Proc 19:421-3
Hadley, G A; Snider, M E; Steinmuller, D (1987) Strain differences in the expression of the Epa-1-restricting element. J Immunogenet 14:149-58