Suppression of Lymphocyte Activation by A Protein Released From Isolated Perfused Rat Liver

Abstract

Isolated rat liver perfusates contain a substance which inhibits ³H–thymidine uptake by phyto–hemagglutinin–stimulated human peripheral blood lymphocytes in a dose–dependent, noncytotoxic fashion. Suppression is not due to interference of lymphocyte–phytohemagglutinin interaction or dilution of the thymidine pool. Complete inhibition of thymidine uptake is achieved with less than 1.0 fig of material per ml (which is a potentially achievable concentration in vivo). The release of this material is directly and quantitatively associated with hepatocellular injury as measured by release of glutamic pyruvate transaminase. The material is a highly basic protein with a molecular weight of approximately 65,000 to 80,000 daltons. It is a product of the hepatocyte rather than of nonparenchymal liver cells. Liver–derived materials, such as the presently described molecule, may play a role in in situ regulation of lymphocyte function during immunologically mediated liver disease.