Discrepancy between phenotypic and functional features of natural killer T-lymphocytes in B-cell chronic lymphocytic leukaemia

Summary. The phenotypic expression and functional capacity of natural killer (NK) T-lymphocytes (E+, OKT3 +) were analysed in a series of untreated patients with B-cell chronic lymphocytic leukaemia (B-CLL). The mean value of NK activity of B-CLL T-lymphocytes, tested against the K562 cell line, was significantly depressed (P&<0-01) in the 20 cases studied, compared with that of normal T-cells. Incubation with human leucocyte interferon produced an increase (P&< 0-05) in NK activity, although the mean value was still significantly lower (P &< 0-05) than that obtained with normal T-cells. Furthermore, the formation of effector-target conjugates was significantly lower (P&<0-01) among B-CLL T-cells compared with normal T-lymphocytes. Despite the reduced NK functions observed in the majority of B-CLL patients, the capacity of T-cells to react with the monoclonal antibody (MoAb) Leu-7 (HNK-1 clone), assessed in 60 patients, was significantly higher (P&<0.001)in B-CLL than in normal blood (mean 24%± 10.6 SD v 9%± 4.2), irrespective of the clinical stage of the disease. These findings suggest that the reduced cytotoxic ability of B-CLL T-lymphocytes may be due either to an expanded population of immature T-cells which already express a cytotoxic-like phenotype (E +, OKT3 +, HNK-1+) but which lack adequate cytotoxic functions, or, alternatively, to an intrinsic defect of the natural effectors present within the T-cell population of B-CLL. The T-cell functional abnormalities documented in this study, together with other defective functions previously described, may be implicated in some of the complications frequently associated with B-CLL, particularly the high incidence of secondary neoplasms. There is growing evidence that natural cytotoxicity may play a major role in the immune surveillance system, both against tumour cells and virus-infected cells (Herberman & Ortaldo, 1981).Natural killer (NK) cells are a morphologically homogeneous population of large granular lymphocytes with azurophilic granules in the cytoplasm (Timonen et al, 1981), which are non-adherent and express receptors for the Fc portion of IgG. About 50% of these cells form rosettes with sheep red blood cells (E-rosettes) (West et al, 1977). A monoclonal antibody (MoAb) which appears to react with practically all human NK cells (HNK-1 clone, Leu-7: Becton Dickinson) has been recently produced (Abo & Balch, 1981). Purification experiments have shown that in man the NK activity is present within two distinct HNK-1 positive lymphocyte subsets: HNK-1+, OKT3 (pan T)-, OKMl (myelo-monocytic antigen)+ and HNK-1 +, OKT3 +, OKMl- (Abo et al, 1982). Abnormal levels of natural cytotoxicity have been reported in numerous human conditions. More recently the abnormal proliferation of T-cells with NK function has been reported in cases of acute and chronic T-cell leukaemias (Komiyama et al, 1982: Itoh et al, 1983). B-cell chronic lymphocytic leukaemia (B-CLL) is a neoplastic disorder characterized by the progressive accumulation of monoclonal B-lymphocytes (Preud'homme & Seligmann, 1972), often complicated by severe hypogammaglobulinaemia (Foa et al. 1979) and by a high risk of second tumours (Hyman, 1969). Recent evidence indicates that, together with the neoplastic B-cell proliferation, several phenotypic and functional abnormalities can be encountered within the residual T-cell population (Kay et al, 1979; Chiorazzi et al, 1979; Lauria et al, 1980; Foa et aZ, 1980; Davis, 1981). This has lead several authors to suggest that these abnormalities may play a role in the progression of the disease and in the development of some of its complications. In view of this we have tested the reactivity of the T-cell enriched population from 60 cases of B-CLL with the HNK-1 MoAb. In a series of patients the phenotypic analysis was compared with the NK activity measured in a chromium release assay, before and after pre-incubation with human leucocyte interferon (IFN), and by the capacity to form conjugates with NK sensitive target cells.