Abstract

The object of this program project is to apply new technological advances in basic immunology, the production of monoclonal antibodies and T cell clones to help develop protocols for the induction of tissue transplantation tolerance in humans. Our preliminary studies suggest that preparation of cadaver renal transplant recipients with total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) can markedly reduce, or perhaps eliminate, the requirement for chronic immunosuppressive drug therapy. The proposed project attempts to use mouse monoclonal antibodies to human T cells as new therapeutic agents (to replace the polyclonal rabbit ATG) and as new diagnostic agents (to monitor changes in T cell subsets). A variety of monoclonal antibodies to human T cells will be generated and analyzed for their capacity to identify new subsets which play important roles in transplantation immunity. We will study the mechanism of action of the suppressor cells and search for suppressive lymphokines. Cloned human suppressor cells will also be used as immunogens in order to generate mouse monoclonal antibodies to surface markers which are unique to these suppressor cell subpopulations.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Program Projects (P01)
Project #
5P01AM032075-03
Application #
3092271
Study Section
Transplantation and Immunology Committee (TIC)
Project Start
1983-01-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Weyand, C M; Goronzy, J; Swarztrauber, K et al. (1989) Immunosuppression by anti-CD4 treatment in vivo. Persistence of secondary antiviral immune responses. Transplantation 47:1034-8
Weyand, C M; Goronzy, J; Swarztrauber, K et al. (1989) Immunosuppression by anti-CD4 treatment in vivo. Cellular and humoral responses to alloantigens. Transplantation 47:1039-42
Adkins, B; Gandour, D; Strober, S et al. (1988) Total lymphoid irradiation leads to transient depletion of the mouse thymic medulla and persistent abnormalities among medullary stromal cells. J Immunol 140:3373-9
Alpert, S D; Turek, P J; Foung, S K et al. (1987) Human monoclonal anti-T cell antibody from a patient with juvenile rheumatoid arthritis. J Immunol 138:104-8
Lowder, J N; Miller, R A; Hoppe, R et al. (1987) Suppression of anti-mouse immunoglobulin antibodies in subhuman primates receiving murine monoclonal antibodies against T cell antigens. J Immunol 138:401-6
Takada, S; Engleman, E G (1987) Evidence for an association between CD8 molecules and the T cell receptor complex on cytotoxic T cells. J Immunol 139:3231-5
Foung, S K; Blunt, J; Perkins, S et al. (1986) A human monoclonal antibody to rhG. Vox Sang 50:160-3
Goronzy, J; Weyand, C M; Fathman, C G (1986) Long-term humoral unresponsiveness in vivo, induced by treatment with monoclonal antibody against L3T4. J Exp Med 164:911-25
Mohagheghpour, N; Damle, N K; Takada, S et al. (1986) Generation of antigen receptor-specific suppressor T cell clones in man. J Exp Med 164:950-5
Foung, S K; Taidi, B; Ness, D et al. (1986) A monoclonal antibody against HLA-A11 and A24. Hum Immunol 15:316-9

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