Scand. J. Immunol. 21, 315-320, 1985 Impaired Gamma Interferon Production by Cells from Patients with Lymphoproliferative Disorders of Mature T and NK Cells F. PANDOLFI, M. CAPOBIANCHI, P. MATRICARDI, J. FACCHINl, G. BONOMO, G. DE ROSSI, G. SEMENZATO, M. FIORILLI, F. DIANZANI & F. AIUTI Department of Allergology and Clinical Immunology, Department of Virology, and Department of Haematology, 'La Sapienza' University, Rome, and Department of Clinical Medicine, University of Padua, Padua, Italy Pandolfi, F., Capobianchi, M., Matricardi, P., Facchini, J., Bonomo, G., De Rossi, G., Semenzato, G , Fiorilli, M., Dianzani, F. & Aiuti,. F. Impaired Gamma Interferon Production by Cells from Patients with Lymphoproliferative Disorders of Mature T and NK Cells. Scand. J. Immunol. 21, 315-320, 1985. We investigated interferon (IFN) production by peripheral blood mononuclear cells from four patients with chronic 0KT4 T-lymphocytic leukaemia and three patients with abnormal expansions of granular lymphocytes. No spontaneous production of IFN-y 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-y 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-y) induced considerable IFN-y 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-y, this is not a general mechanism that underlies the disease. In fact, in all our cases a defect of IFN-y production was found. This defect seems due to an alteration at the membrane level of the galactose-containing glycoproteins and ean be restored by induction with a calcium ionophore. F. Pandolfi, Department of Clinical Immunology, Viale dell'Universita 37, 00185 Rome, Italy In recent years there has been considerable interest in adult patients with lymphoprolifera- tive disorders of T or natural killer (NK) cells, usually referred to as chronic T-cell lymphocy- tic leukaemia (T-CLL) [20] or abnormal ex- pansions of granular lymphocytes (GL) [19]. It has been shown that cells from these patients represent expansions of mature T or NK cellular subpopuiations capable of specialized functions [17]. These cases, although rare, are remarkable, since they may represent models for the study of T and NK cellular biology. In addition, new findings have come to light in the search for possible aetiological or pathogenetic factors in these disorders. The most remarkable achievement has been the isolation of a new type-C retrovirus (human T-cell leukaemia virus (HTLV)) in Japanese and West Indian patients with a unique T leukaemia usually referred to as adult T-cell leukaemia (ATL) [6]. Research has also been carried out on malignant T cells to evaluate the production of lymphokines perhaps related to cell activation or growth. It is known [6] that ATL cells produce and respond in vitro to interleukin-2 (IL-2), an inducer of T and NK 315