Abstract

The beneficial effect of preoperative blood transfusions (random or donor-specific) on the survival of renal transplants (cadaver or living related) has been well documented. The mechanism(s) however are unknown despite extensive research. We will use the well defined donor-specific blood transfusion model in selected living related combinations in an attempt to identify mechanisms which contribute to the spectacular success of this model. We hope that the information obtained can be extended to the situation in which random blood transfusions are given. It is planned to investigate in detail 6 potential mechanisms in the donor-specific transfusion system. 1) Selection into high and low responders, 2) induction of unresponsiveness, 3) activation of specific and non-specific suppressor cells, 4) induction of antibodies, 5) immunomodulation of the recipient, and 6) in situ allograft changes. In vitro test systems such as MLC, CML, PLT, immunofluorescence, HLA serology, and monitoring of lymp]hocyte subsets with monoclonal antibodies will be used. In addition, the in situ allograft reaction will be investigated using fine needle aspiration cytology utilizing recently developed techniques of labelling cytocentrifuge preparations with monoclonal and anti-HLA-A, B, C, DR and Beta-2 antisera. The information gained from these experiments will be utilized to optimize the donor-specific blood transfusion protocol in an attempt to decrease sensitization, determine the effectiveness of immunosuppression during the administration of blood transfusions, and additionally come to conclusions about the mechanisms of random donor transfusions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK031774-06
Application #
3230315
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1983-01-01
Project End
1990-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Kusaka, S; Grailer, A P; Fechner Jr, J H et al. (1995) Evidence for a possible Th2 bias in human renal transplant tolerance. Transplant Proc 27:225-6
Burlingham, W J; Grailer, A P; Fechner Jr, J H et al. (1995) Microchimerism linked to cytotoxic T lymphocyte functional unresponsiveness (clonal anergy) in a tolerant renal transplant recipient. Transplantation 59:1147-55
DeVito-Haynes, L D; Jankowska-Gan, E; Sollinger, H W et al. (1994) Monitoring of kidney and simultaneous pancreas-kidney transplantation rejection by release of donor-specific, soluble HLA class I. Hum Immunol 40:191-201
Geissler, E K; Wang, J; Fechner Jr, J H et al. (1994) Immunity to MHC class I antigen after direct DNA transfer into skeletal muscle. J Immunol 152:413-21
DeVito, L D; Hogan, K T; Mason, B P et al. (1993) Epitope fine specificity of human anti-HLA-A2 antibodies. Transplant Proc 25:189-90
Niguma, T; DeVito, L D; Grailer, A P et al. (1993) HLA-A2-specific antibody production in severe combined immunodeficient mice reconstituted with human peripheral blood leukocytes from HLA-presensitized donors. Transplant Proc 25:239-40
De Vito, L D; Mason, B P; Jankowska-Gan, E et al. (1993) Epitope fine specificity of human anti-HLA-A2 antibodies. Identification of four epitopes including a haptenlike epitope on HLA-A2 at lysine 127. Hum Immunol 37:165-77
Niguma, T; DeVito, L D; Grailer, A P et al. (1993) Activation of HLA-A2-specific memory B cells in severe combined immunodeficient mice. Hum Immunol 37:7-16
Burlingham, W J; Fechner, J H; DeVito, L D et al. (1993) Human interleukin-2 and lymphoproliferative (T-helper cell) responses to soluble HLA class I antigens in vitro: I. Specificity for polymorphic domains. Tissue Antigens 42:35-8
Kawamura, T; Niguma, T; Fechner Jr, J H et al. (1992) Chronic human skin graft rejection in severe combined immunodeficient mice engrafted with human PBL from an HLA-presensitized donor. Transplantation 53:659-65

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