T lymphocytes from alcoholic cirrhotic patients show normal interleukin-2 production but a defective proliferative...

T lymphocyte proliferation is a complex process involving intra- and extracellular molecules. T cell activation was studied in T lymphocytes from patients with alcoholic cirrhosis. A defective phytohemagglutinin (PHA)-induced T cell mitogenesis was observed in 60% of these patients. Likewise, their blastogenic response to anti-CD3 was also depressed (p < 0.05). However, the DNA synthesis induced by stimulation with phorbol esters (12-O-tetradecanoil-phorbol-13-acetate) + ionomycin was normal (p > 0.05). These alterations cannot be ascribed either to decreased interleukin-2 synthesis or to a defective interleukin-2 receptor expression after cellular activation. Moreover, supplementation of the PHA-stimulated T cell cultures with saturant concentrations of recombinant interleukin-2 did not normalize the hypoproliferative response of T cells from alcoholic++ cirrhotic patients. These results provide evidence that a generalized alteration in the interactions between either mitogens or interleukin-2 and their receptors can explain the T lymphocyte-defective blastogenesis found in patients with alcoholic cirrhosis.