Current clinical immunosuppressive regimens for allograft recipients affect the entire immune response and result in many unwanted side effects.
The first aim of this research is to determine which T lymphocyte subsets are essential for rejection of skin and heart allografts in the mouse. In particular, we will try to separate the roles of class I antigen-reactive T cells (cytotoxic/suppressor cells) from class II antigen-reactive T cells (helper cells). We will then use monoclonal antibodies against the appropriate T cell subsets as therapeutic reagents for normal mouse recipients of skin and heart allografts. Another specific aim is to determine whether some monoclonal antibody isotypes are more effective than others and whether treating with more than one isotype at a time might be helpful. We will assess the extent to which monoclonal antibody induces modulation of T cell surface antigens; we will try to compensate for modulation and loss of immunosuppressive effect by conjugating the monoclonal antibodies with the plant toxin ricin. Finally, we will determine the conditions under which infusion of donor strain lymphocytes (B cell and T cell subsets) into the recipient, after treatment with monoclonal antibody and allografting, affects establishment of microchimerism (in spleen and lymph nodes) and long term allograft survival.
| Smith, D M; Stuart, F P; Wemhoff, G A et al. (1988) Cellular pathways for rejection of class-I-MHC--disparate skin and tumor allografts. Transplantation 45:168-75 |
