Impaired gamma interferon production by cells from patients with lymphoproliferative disorders of mature T and NK cells.
We investigated interferon (IFN) production by peripheral blood mononuclear cells from four patients with chronic OKT4 T-lymphocytic leukaemia and three patients with abnormal expansions of granular lymphocytes. No spontaneous production of IFN-gamma was found in supernatants of cultures from both patients and normal controls. However, whereas the enzyme galactose oxidase or staphylococcal enterotoxin B was able to induce IFN-gamma production by normal cells, no production could be obtained in the cells under study. The possibility that this lack of production might have been attributed to an excess of N-acetylneuraminic acid masking galactose residues or to a defect of monocyte accessory cells was ruled out either by pre-treating the cells with neuraminidase or by adding normal adherent cells to the cultures, both of which resulted in a lack of production. On the contrary, the calcium ionophore A23187 (considered to act as a second specific step, following oxidation of galactose residues, toward genetic derepression of IFN-gamma) induced considerable IFN-gamma production in all the three tested patients. It can be concluded that, although in rare cases, as previously reported by other authors, cells from patients with T or NK lymphoproliferative disorders may spontaneously produce IFN-gamma, this is not a general mechanism that underlies the disease. In fact, in all our cases a defect of IFN-gamma production was found. This defect seems due to an alteration at the membrane level of the galactose-containing glycoproteins and can be restored by induction with a calcium ionophore.
D000328:Adult; D000368:Aged; D002118:Calcium / Q000494:pharmacology; D005260:Female; D005692:Galactose Oxidase / Q000494:pharmacology; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis*; D007476:Ionophores / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D007945:Leukemia, Lymphoid / Q000097:blood*; D008218:Lymphocytosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D007370:Interferon Type I; D007476:Ionophores; D007371:Interferon-gamma; D005692:Galactose Oxidase; D002118:Calcium