Recent investigations in these laboratories have revealed that dietary nucleotides are required for the maintenance of cellular immunity. A nucleotide free diet (NFD) suppresses allograft rejection, increases length of survival following bone marrow transplantation, and retards development of delayed cutaneous hypersensitivity. In vivo and in vitro studies suggest the T lymphocyte is the target of this nucleotide deprivation. Recently completed studies reveal that the nucleotide free diet enhances the efficacy of the potent new immunosuppressant cyclosporine. Lymphoid derived tumor cells also are dependent upon a nucleotide base source in the diet. This proposal seeks both to identify the T lymphocyte subpopulation vulnerable to dietary nucleotide deprivation and to discover the purine or pyrimidine base required for normal immunity. Additional studies will determine the efficacy of the NFD in the treatment of various T and B cell lymphomas. Clinical relevant applications include further exploration of synergism between dietary nucleotides and immunosuppressive drugs in the prevention of allograft rejection and between antimetabolites used in cancer treatment. This proposal offers an important new therapeutic advance for the treatment of whole organ and bone marrow transplant recipients, cancer patients, and critically ill patients requiring intensive nutritional support.
