Purine metabolism in human T lymphocytes: role of the purine nucleoside cycle

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Abstract
Human intrathymic T lymphocytes were separated by a bovine serum albumin density gradient into a population of G1-phase small thymocytes and a population of S-phase-enriched large thymocytes. Purine metabolism was studied in these thymocyte populations, representing immature T lymphocytes and compared with the metabolism of mature T lymphocytes isolated from the peripheral blood. De novo purine biosynthesis was highly cell cycle dependent; i.e., de novo purine biosynthetic activity was found only in large S-phase thymocytes, whereas both G1 T cell populations lacked any significant activity. G1-phase small thymocytes and G1-phase peripheral blood T lymphocytes have only salvage pathways to maintain their purine nucleotide pools. Despite the similarity of purine salvage activities in G1 thymocytes and in peripheral blood T lymphocytes, small thymocytes have 4-fold lower levels of purine nucleoside triphosphates. The decreased levels of purine nucleotides in G1 thymocytes may be the result of increased purine efflux. A unusually large proportion (24-48%) of hypoxanthine incorporated by G1 thymocytes is excreted into the medium in the form of inosine.