Engagement of the T cell receptor/CD3 complex activates the serine/threonine kinase, Raf‐1, but the physiologic consequences of its activation have not been determined. The effects of Raf‐1 on interleukin 2 (IL2) production in T cells were examined using activated and inhibitory forms of Raf‐1. A truncated active form of Raf‐1 was expressed constitutively from the metallothionein promoter in a malignant T cell line, Jurkat. Treatment of the cells with zinc and cadmium greatly increased active Raf‐1 expression. This increase in Raf‐1 expression allowed antibodies to CD3 and to CD28 to stimulate IL2 production in the absence of phorbol myristate acetate (PMA) and enhanced IL2 production stimulated by these antibodies in the presence of PMA. The action of active Raf‐1 was to increase IL2 gene transcription as it enhanced transcription of a reporter gene linked to IL2 promoter. Finally, the dominant negative form of Raf‐1 inhibited transcription directed by the IL2 promoter that was induced by the mitogen phytohemagglutinin (PHA) and PMA. We conclude that Raf‐1 activity is necessary for IL2 gene transcription and secretion. These data indicate a role for Raf‐1 in the immune response.

Porcine hepatocytes are currently being investigated as a therapy for patients suffering from acute liver failure. Incorporating hepatocytes in an extracorporeal device that would stabilize a patient until transplantation or recovery could dramatically decrease the mortality rate associated with this disease. The ability to maximize hepatocyte function would contribute significantly to being able to provide the required cell mass in a device of reasonable size. Several approaches have been effective at increasing rat hepatocyte function in vitro, including coculture with nonparenchymal cells. In this study, we investigated the effect of the addition of 3T3 cells to porcine hepatocyte culture and found that while there was an increase in albumin secretion, there was little or no effect on urea synthesis or cytochrome P450 activity.