Abstract

The proposed research is aimed towards the definition of organ-specific non-MHC-coded alloantigens of human renal, cardiac and B-lymphocyte tissues. Our preliminary findings for such an antigenic system in human kidneys and their possible role in allograft failure will be expanded to renal, cardiac transplants using eluates prepared from rejected grafts, longitudinal screening of the serum samples, and preparation of both hetero and monoclonal (mouse-mouse and mouse-human heterohybridomas) antibodies defining organ-specific antigens. The target cells will include renal and cardiac biopsy tissues in addition to normal fibroblasts and human mononuclear cell population prepared from peripheral blood. The serological specificities of the antigens and their exact cellular localization will be defined by immunofluorescence, immunoperoxidase and electron microscopic analysis. An attempt will also be made towards cell surface labeling of these antigens followed by immunoprecipitation and characterization on SDS-PAGE. Relationship between organ-specific antigens and MHC-coded alloantigens and their interrelationship in eliciting an immune response against organ-specific antigens will be investigated. In addition, the antigenic determinants defined by the pretransplant B-cell reactive """"""""enhancing"""""""" type of antibodies will be identified and immunochemically characterized.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK032253-03
Application #
3230686
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1983-12-01
Project End
1987-04-30
Budget Start
1985-12-01
Budget End
1987-04-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Virginia Commonwealth University
Department
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298

  Publications

Smith, Craig R; Jaramillo, Andres; Poindexter, Nancy J et al. (2002) In vitro T cell proliferation from kidney allograft biopsies with unremarkable pathology: new strategies for an old problem. Transplantation 73:142-5
Smith, C R; Mohanakumar, T; Shimizu, Y et al. (2000) Brief cyclosporine treatment prevents intrathymic (IT) tolerance induction and precipitates acute rejection in an IT rat cardiac allograft model. Transplantation 69:294-9
SivaSai, K S; Jendrisak, M; Duffy, B F et al. (2000) Chimerism in peripheral blood of sensitized patients waiting for renal transplantation: clinical implications. Transplantation 69:538-44
Sivasai, K S; Mohanakumar, T; Phelan, D et al. (2000) Cytomegalovirus immune globulin intravenous (human) administration modulates immune response to alloantigens in sensitized renal transplant candidates. Clin Exp Immunol 119:559-65
SivaSai, K S; Mohanakumar, T; Phelan, D et al. (1999) Down regulation of in vivo and in vitro T cell responses post cytomegalovirus immune globulin intravenous (human) administration in sensitized renal transplant candidates. Transplant Proc 31:1378-81
Shenoy, S; Mohanakumar, T; Todd, G et al. (1999) Immune reconstitution following allogeneic peripheral blood stem cell transplants. Bone Marrow Transplant 23:335-46
Poindexter, N J; Steward, N S; Mohanakumar, T (1999) Characterization of an HLA-A3 restricted human kidney specific T cell clone. Hum Immunol 60:939-43
Shenoy, S; Desch, K; Duffy, B et al. (1998) Analysis of graft-versus-host disease (GVHD) and graft rejection using MHC class I-deficient mice. Clin Exp Immunol 112:188-95
Burlingham, W J; Grailer, A P; Heisey, D M et al. (1998) The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors. N Engl J Med 339:1657-64
Poindexter, N; Shenoy, S; Howard, T et al. (1997) Allograft infiltrating cytotoxic T lymphocytes recognize kidney-specific human minor histocompatibility antigens. Clin Transplant 11:174-7

Showing the most recent 10 out of 28 publications