Effector mechanisms in murine allograft rejection: comparison of skin and heart grafts in fully allogeneic and minor histocompatibility antigen-mismatched strain combinations.

Cytotoxic T lymphocytes (CTLs) and macrophage-mediated delayed-type hypersensitivity (DTH) responses may both mediate allograft rejection. Furthermore, although allograft rejection is classically considered a type [22, 23, 38, 50, 52] 1 cellular immune response, type-2 cytokines can support rejection. This study examines whether the immunogenicity of the transplanted tissue, as determined by type of tissue (skin versus heart) and degree of antigenic mismatch, influences recruitment of these effector mechanisms. Graft survival, histological appearance and intragraft gene expression (IL-2, IFN-gamma, IL-12 p40, IL-4, IL-10, perforin, Fas ligand (Fas L), iNOS and TNF-alpha) were compared for fully allogeneic, minor histocompatibility (mHC) antigen-mismatched and syngeneic skin and heart grafts. We found mRNA characteristic of CTLs and DTH responses in fully allogeneic and mHC antigen-mismatched skin and heart grafts. Concomitant type-1 and type-2 cytokine gene transcription was seen. These findings demonstrate that the tissue grafted and degree of antigenic disparity between donor and recipient do not restrict the repertoire of cellular immune responses involved in graft rejection. This finding has implications in the design of new immunosuppressive strategies for clinical transplantation.