T lymphocytes from alcoholic cirrhotic patients show normal interleukin-2 production but a defective proliferative response to polyclonal mitogens.
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.
Girón-González
J A
JA
Department of Internal Medicine, Universidad de Cádiz, Spain.
Alvarez-Mon
M
M
Menéndez-Caro
J L
JL
Manzano
L
L
Abreu
L
L
Yebra
M
M
Durántez-Martínez
A
A
D000906:Antibodies / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008104:Liver Cirrhosis, Alcoholic / Q000276:immunology*; D008213:Lymphocyte Activation; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D017252:CD3 Complex; D007376:Interleukin-2; D008934:Mitogens; D010703:Phorbol Esters; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D015759:Ionomycin; D004247:DNA