Impaired Gamma Interferon Production by Cells from Patients with Lymphoproliferative Disorders of Mature T and NK Cells

Abstract

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‐γ 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‐γ 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‐acetylneuramic 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‐γ) induced considerable IFN‐γ 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‐γ, this is not a general mechanism that underlies the disease. In fact, in all our cases a defect of IFN‐γ 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.